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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/cm 2 nickel sulphate, and the same skin areas were then re-exposed to 0.2, 0.5, 12.8 and 370 μg/cm 2 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/cm 2 ) 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/cm 2 , 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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current cosmetic regulations primarily focus on protecting consumers, not the professional user who is subjected to a partly different, and certainly more intense exposure to hazardous substances. Against this background, this systematic review aims to compile and appraise evidence regarding skin toxicity of 2-hydroxyethyl methacrylate (HEMA; CAS no. 212-782-2) and ethyl cyanoacrylate (ECA; CAS no. 7085-85-0) contained in cosmetic glues used among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. This systematic review followed the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) 2020 recommendations for reporting systematic reviews and meta-analysis. In total, six publications from six countries were eligible for this systematic review. A meta-analysis revealed that hairdressers and beauticians have a ninefold increased risk of developing contact allergy to HEMA compared with controls who are not hairdressers and beauticians. Results for ECA are lacking. The results of this systematic review clearly show that-regarding contact allergy to acrylates-it is not appropriate to apply risk assessment for consumers to hairdressers and beauticians who occupationally handle cosmetic glues. The regulations in existence do not adequately address occupational risks for hairdressers and beauticians connected with the use of acrylate-containing cosmetic substances and need reconsideration., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Studies on the causes and consequences of occupational contact dermatitis (OCD) among young workers are non-existent., Objectives: Determine causes and consequences of OCD among workers younger than 35 years of age., Methods: A questionnaire was sent to 6251 workers younger than 35 years at notification with recognized OCD (response rate 47%)., Results: The most prevalent occupations were health care workers, kitchen workers, nursery teachers, and hairdressers and beauticians. Seventy-six percent still had eczema, and 77% of these had eczema half to all the time over the last 3 months, with 61% evaluating their eczema as moderate to very severe. Fifty-three percent had changed their occupation since notification, and 42.5% had lost their job because of OCD. Allergic OCD increased the odds ratio (OR) for facial or foot eczema, job loss, change in work tasks, difficulties finding work, decrease in income, and sick leave. Age at notification of 25 years of age or younger increased the risk of job loss and feeling restricted in choice of job. Workers in the food industry had a higher OR for job loss, whereas hairdressers and beauticians had a higher risk of job loss and a decrease in income., Conclusions: The severe, long-term consequences of OCD notification signify the need for further preventive strategies among young workers., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hairdressers are at high risk of developing occupational hand eczema. Opinions on the health and safety concerns of nonfood consumer products, such as cosmetics and their ingredients, consider the exposure of a "common consumer," which may not account for occupational exposure of hairdressers. As a result, there is a parlous scenario in which serious safety concerns about occupational exposures are present. The purpose of this review is to compare the frequency of exposure to various types of hair cosmetic products among hairdressers and consumers. Database searches for this review yielded a total of 229 articles; 7 publications were ultimately included. The analysis showed that-dependent on the task-hairdressers were exposed 4 to 78 times more than consumers to a wide spectrum of hair cosmetic products used in their daily working life, ranging from shampoos, conditioners, oxidative and nonoxidative hair colors, to bleaching agents. The highest frequency was found for coloring hair with oxidative hair color. Consumer use frequency does not appear to be appropriate for representing hairdresser exposure. The current standards do not effectively address the occupational risks associated with hairdressers' use of cosmetics. The findings of this study should cause current risk-assessment procedures to be reconsidered., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Hairdressers are commonly affected by hand eczema (HE) due to skin hazardous exposure such as irritants and allergens in the work environment., Objective: To give an overview of the current prevalence, incidence, and severity, as well as the pattern of debut and the contribution of atopic dermatitis on HE in hairdressers., Methods: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed. Studies published from 2000 to April 2021 that fulfilled predefined eligibility criteria were retrieved., Results: A pooled lifetime prevalence of 38.2% (95% confidence interval [CI] 32.6-43.8), a pooled 1-year prevalence of 20.3% (95% CI 18.0-22.6), and a pooled point prevalence of 7.7% (95% CI 5.8-9.6) of HE was observed in hairdressers. The lifetime prevalence in fully trained hairdressers and hairdressing apprentices was almost identical. The pooled incidence rate of HE was 51.8 cases/1000 person-years (95% CI 42.6-61.0) and the pooled prevalence of atopic dermatitis was 18.1% (95% CI 13.6-22.5)., Conclusion: HE is common in hairdressers and most hairdressers have debut during apprenticeship. The prevalence of atopic dermatitis in hairdressers is comparable with estimates in the general population, indicating that occupational exposures are the main factor in the increased prevalence of HE in hairdressers. This warrants a strategic and collective effort to prevent HE in hairdressers., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergic contact dermatitis (ACD) is classically described as a delayed-type hypersensitivity reaction. However, patients often experience flare-ups characterized by itching erythema, edema, and often vesicles occurring within hours after re-exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin-resident memory T (T RM ) cells play a central role in ACD. However, the pathogenic role of T RM cells in allergen-induced flare-ups is not known., Methods: By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal T RM cells in flare-up reactions to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of T RM cells, neutrophils, and CXCL1/CXCL2 in the response., Results: We show that CD8 + T RM cells initiate massive infiltration of neutrophils in the epidermis within 12 h after re-exposure to the contact allergen. Depletion of neutrophils before re-exposure to the allergen abrogated the flare-up reactions. Furthermore, we demonstrate that CD8 + T RM cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C-X-C chemokine receptor type 1 and 2 inhibits flare-up reactions and neutrophil infiltration., Conclusion: As the first, we show that epidermal CD8 + T RM cells cause ACD flare-ups by rapid recruitment of neutrophils to the epidermis., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Parents report that children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing sunscreen following application., Objectives: To evaluate whether contact dermatitis develops following repeated application of aluminium-containing sunscreens in children with aluminium sensitization and vaccination granulomas., Methods: Sixteen children aged 2-9 years (mean age 5 years) with vaccination granulomas and a positive patch test reaction to aluminium chloride hexahydrate 2%/10% petrolatum completed a blinded repeated open application test (ROAT) with two daily applications of two sunscreens for 14 days. One cream contained aluminium and the other did not. The children served as their own controls., Results: Sixteen children completed the study. Only one child (6%) had a positive skin reaction during ROAT on day 2 to the sunscreen with aluminium. None reacted to the sunscreen without aluminium., Conclusions: Use of aluminium-containing sunscreens may on a case basis lead to allergic contact dermatitis in aluminium allergic children., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Facial allergic contact dermatitis caused by cosmetic products is common. New allergens in cosmetics continuously emerge., Objectives: To investigate characteristics of patients with facial dermatitis (FD) between 2010 and 2019 including patch test results from cosmetic-related allergens and a new test series with cosmetic-relevant natural ingredients (CRNIs)., Methods: This is a retrospective study analysing demographics, clinical characteristics according to MOAHLFA index (male; occupation; atopic dermatitis; hand; leg; face; age ≥ 40 years), and patch test results to 27 cosmetic-relevant allergens in FD patients. A prospective study evaluating a screening test series with CRNIs in consecutive FD patients for 1 year was also conducted. These patients received a questionnaire for collecting extra characteristics (eg, concerning quality of life)., Results: Of 8740 tested patients, 2292 (26.2%) had FD. Of these, 30.6% had cosmetic-induced FD. The most common cosmetic-related allergens were fragrances and preservatives. The most common patch test-positive CRNIs were hydroperoxides of limonene and linalool, and propolis. Potato and peanut were rare, but the most common prick test-positive CRNIs, however, without any relation to the use of cosmetic products. FD affected nearly all patients' quality of life and caused limitations to their daily life., Conclusions: Updated management and quick diagnosis of FD is important to avoid negative impact on patients' quality of life., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chromium and cobalt are important skin sensitizers. It has, however, been difficult to identify causative exposures. Studies on nickel allergy have demonstrated piercing as critical for both sensitization and elicitation. It may be speculated that the same applies for chromium and cobalt., Objective: To examine the content and release of chromium and cobalt from earrings randomly purchased in Denmark., Methods: Three hundred four earrings were examined with x-ray fluorescence (XRF) spectrometry. Earrings with measured content of chromium or cobalt were spot tested with diphenylcarbazide spot test (n = 166) or Nitroso-R spot-test (n = 99), respectively. Chromium and cobalt release were quantified in a selected subsample (n = 100) with the artificial sweat test (EN 1811)., Results: Chromium was present in 54.6% (166/304) of earrings and cobalt was present in 72.0% (219/304),- measured by XRF. All chromium spot tests for chromium VI were negative. The cobalt spot test was positive for one component. Chromium release was found from 59/100 (median concentration = -0.06 μg/cm 2 /week) and cobalt release from 29/100 (median concentration = -0.06 μg/cm 2 /week) of earrings in tested subsample., Conclusion: Earrings for piercing release chromium and cobalt and may on a case basis be a source of chromium and cobalt allergy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention., Objectives: To assess whether clinical characteristics, self-reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time., Methods: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age- and sex-matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019., Results: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07-7.08) and hand dermatitis (OR 1.98, 95% CI 1.13-3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P = .5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst-case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018., Conclusion: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recent population-based studies on the incidence rates (IRs) of occupational contact dermatitis (OCD) are sparse., Objectives: To determine the IRs of OCD and development thereof between 2007 and 2018 in known risk occupations., Methods: Data on all recognized cases of OCD were used to calculate IRs as the number of recognized OCD cases per 10 000 workers per year. Asymptotic chi-square test was used to compare the IRs between 2007-2012 and 2013-2018., Results: The median age at notification of OCD was below 30 years for several of the examined occupations. Hairdressers and beauticians, bakers, dentists and dental assistants, and manufacturing of windmills had the highest overall IRs of OCD. We found a statistically significant increase in the IRs of OCD for child/nursery care workers., Conclusions: The median age at notification of OCD was low for several of the occupations, signifying the need for further preventive strategies among young people. Based on the IRs of OCD, future preventive efforts should be directed at hairdressers and beauticians, bakers, dentists and dental assistants, and manufacturing of windmills. Furthermore, the statistically significant increase in IRs of OCD among child/nursery care workers highlights the need for further preventive strategies in this field., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patch testing is the gold standard for identifying culprit allergens in allergic contact dermatitis; however, it is laborious and positive reactions are difficult to quantitate. Development of complementary in vitro tests is, therefore, of great importance., Objectives: This study aimed to improve the in vitro lymphocyte proliferation test (LPT) to detect allergic responses to nickel (Ni), cobalt (Co), and chromium (Cr)., Methods: Twenty-one metal allergic patients with a positive patch test to Ni (n=16), Co (n=8), and Cr (n=3) and 13 controls were included. All were tested by a flow cytometric LPT., Results: Metal-reactive cells were identified as T helper (Th) cells with high expression of the memory marker CD45RO. Skin-homing (cutaneous lymphocyte-associated antigen positive [CLA+]) Ni-reactive memory Th (Th mem hi ) cells identified individuals with a positive patch test for Ni with 100% sensitivity (95% confidence interval [CI] 81%-100%) and 92% specificity (95% CI 67%-100%). Moreover, Co-specific Th mem hi cells expressing CCR6 identified patients with a positive patch test for Co with 63% sensitivity (95% CI 31%-86%) and 100% specificity (95% CI 77%-100%). In Cr allergic individuals, Cr-reactive Th mem hi cells tended to increased CLA and CCR6 expression., Conclusion: Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) has been the most reported fragrance chemical for two decades and will be prohibited in cosmetic products from August 2021., Objectives: To describe the time trend of HICC contact allergy in European patients with dermatitis in 2009 to 2019, and the added value of testing HICC separately in the baseline series., Methods: Data were reviewed for 124 472 patients with dermatitis who were patch tested with HICC 5% pet. in the baseline series in the European Surveillance System on Contact Allergy (ESSCA) network (2009 to 2018) and at the Herlev-Gentofte Hospital Department of Dermatology and Allergy (2009 to 2019)., Results: Contact allergy to HICC was found in 1.98% of 9865 patients in Gentofte and 1.62% of 114 607 patients in the ESSCA network. Overall, the prevalence decreased annually, with 0.156 percentage points (P = .001) in Gentofte and 0.051 percentage points (P = .0002) in ESSCA. The frequency of missed contact allergy to HICC when testing only with fragrance mix II (FMII) was 0.17% (17/9865) and 0.35% (405/114607) of the whole test population in the Gentofte and ESSCA populations, respectively., Conclusions: This is the first study to demonstrate a significant decline in HICC allergy in European patients with dermatitis, most likely attributed to the upcoming European ban., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Occupational contact dermatitis (OCD) is the most commonly recognized occupational disease in Denmark., Objectives: To examine the impact of recognized OCD on degree of employment, sick leave, unemployment, and job change., Methods: Data on all recognized individuals with OCD notified in Denmark between 2010 and 2015 (n = 8940) were linked to information on social transfer payments in the years before and after notification. The number of weeks on unemployment benefits or sick leave and the degree of employment during the 2 years prior to notification was compared with the 2 years following notification., Results: The degree of employment decreased on average 8.9 work-hours/month, corresponding to an average annual loss of income per worker of approximately €1570. The average number of weeks that workers were receiving unemployment benefits and paid long-term sick leave rose by 2.5 and 3.4 weeks, respectively, corresponding to an average additional annual cost per worker of approximately €420 and €770, respectively. Longer case-processing time was significantly associated with lower degree of employment and higher levels of unemployment and sick leave., Conclusions: OCD has a significant negative impact on employment and economics, thus highlighting the need for a national, strategic action plan for effective prevention of OCD., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: In 2005, methylisothiazolinone (MI) was allowed as a stand-alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave-on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave-on cosmetics and reduced the allowed concentration in rinse-off products., Objective: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time., Methods: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events., Results: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7-3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P < .01) was observed, although a decline in the absolute number of patch-test positive patients was seen from 2013 and onward. A reduction in leave-on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P < .01)., Conclusion: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch-tested population has not returned to its pre-epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave-on cosmetics as a source of exposure in MI allergic patients. The process of post-marketing risk assessment of contact allergens in the European Union needs improvement., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series., Objectives: To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments., Methods: Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control., Results: In the 4 years (2015-2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), and Myroxylon pereirae resin (balsam of Peru; 5.8%)., Conclusions: While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS., (© 2020 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: The number of patients with contact dermatitis from glucose sensors and insulin infusion sets is increasing. Patch testing is challenging because of a lack of information concerning the constituent materials of medical devices., Objectives: To report on products and causes of allergic reactions to glucose sensors or insulin infusion sets over a 5-year period and suggest a short screening series., Methods: Analysis of patch test data from consecutive patients suspected of allergic contact dermatitis (ACD) to glucose sensors and/or insulin infusion sets from 2015-2019., Results: Patient numbers increased from 4 to 15 per year; 30/38 (78.9%) were children. In 29 (76.3%), a diagnosis of allergic/probable ACD was established, mostly due to the tapes of the device or allergens in these tapes (n = 23) followed by allergens in the device housing (n = 10). Isobornyl acrylate, abitol, and colophonium were the most common allergens. Information from manufacturers was often difficult to obtain and, if accessible, inadequate. For this reason, the diagnosis was delayed for more than 1.5 years in 12 (31%) patients., Conclusions: The increasing number of patients, mostly children, with ACD from devices used in treatment of type 1 diabetes demonstrates the importance of this problem. Allergies can easily be overlooked, due to the lack of mandatory labeling of the constituent materials of the devices., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Naturally derived cosmetic product ingredients of both plant and animal origin are being included increasingly in product formulations in order to cater to consumer preferences. They may be an overlooked cause of reactions to cosmetic products in some patients with dermatitis., Objectives: To identify naturally derived cosmetic product ingredients with allergenic potential (type I and type IV) and propose a cosmetic screening test series., Methods: The study was conducted in two steps. The first step was a market survey using a nonprofit application helping consumers avoid problematic substances in cosmetic products. The application contained 10 067 cosmetic products that were label checked for naturally derived cosmetic product ingredients. The second step was a literature search to examine how frequently the naturally derived ingredients were described and related to allergic reactions in cosmetics or other topically administered products., Results: We identified 121 different naturally derived cosmetic product ingredients that were included in at least 30 cosmetic products. In total, 22 ingredients were selected for a screening test series., Conclusions: We propose a supplemental patch test and a prick test screening series with naturally derived cosmetic product ingredients for patients with skin reactions to cosmetic products, aiming to identify a cause in more patients than is currently possible., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Aluminum contact allergy is mostly seen in children with vaccination granulomas, following immunization with aluminum-adsorbed childhood vaccines., Objectives: To characterize a cohort of children with vaccination granulomas and aluminum allergy concerning early life conditions, exacerbating factors, avoidance behavior, treatments, and potential impact on quality of life., Methods: A questionnaire study was conducted among 177 children aged 0 to 15 years with vaccination granulomas and aluminum allergy, and a reference group of 61 children aged 3 to 14 years with various types of dermatitis undergoing patch testing., Results: All children in the granuloma group were reportedly affected by itch. Infection exacerbated the itch in 59%. Other worsening factors were eating tin-foiled/canned food (31%) and use of aluminum-containing sunscreen (46%). Many parents took precautions to avoid aluminum exposure. Children with granulomas were more likely to be nonadherent to the National Vaccination Program than the reference group (27% vs 2%, P < .001). Parents in the granuloma group reported a decreased life quality for both parents and children compared with the reference group., Conclusions: Itching vaccination granulomas and aluminum allergy have a considerable negative impact on affected children and their families, causing avoidance behavior, reduced adherence to vaccination programs, and a negative effect on the overall life quality., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The skin is our interface with the outside world, and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (T RM ) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T-cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen DNFB results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8 + CD69 + CD103 + T RM cells in mice. By studying knockout mice, we provide evidence that CD8 + T cells are required for the displacement of the DETC and that DETC are not required for recruitment of CD8 + T RM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8 + epidermal T RM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8 + epidermal T RM cells persist in the epidermis, we show that CD8 + epidermal T RM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cobalt contact allergy is common, but clinical relevance is often difficult to determine., Objectives: To examine the aetiology, prevalence and clinical characteristics of cobalt-allergic patients who were patch tested between 2002 and 2017 at the Department of Dermatology and Allergy, Herlev-Gentofte Hospital., Methods: Patch test data, along with patient characteristics and causative exposures, from all adult dermatitis patients seen and tested between 2002 and 2017 were analysed. Associations were tested with the χ 2 test and logistic regression., Results: A total of 13 475 adults aged 18 to 99 years were patch tested. The overall prevalence of cobalt allergy and the prevalence of isolated cobalt allergy were 3.3% and 1.5%, respectively. The prevalence of isolated cobalt allergy decreased from 2.4% in 2006 to 2009 to 1.1% in 2014 to 2017 (P trend = 0.00003). Leather exposure as a relevant cause of allergic cobalt dermatitis increased from 3.7% in 2002 to 2009 to 8.3% in 2010 to 2017 (P = 0.04). The current clinical relevance of positive patch test reactions, that is, a positive reaction to cobalt combined with a history of current skin exposure to a source of cobalt, was 20.1%., Conclusions: We conclude that cobalt allergy is relatively common, but causative exposures are largely unknown, and the proportion of positive patch test reactions with clinical relevance is low. It is therefore currently unclear how we can better protect consumers and workers from cobalt exposure., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nickel is the most frequent cause of contact allergy worldwide and has been studied extensively. This clinical review provides an updated overview of the epidemiology, exposure sources, methods for exposure quantification, skin deposition and penetration, immunology, diagnosis, thresholds for sensitization and elicitation, clinical pictures, prevention, and treatment. The implementation of a nickel regulation in Europe led to a decrease in the prevalence of nickel allergy, and changes in the clinical picture and disease severity. Nevertheless, the prevalences of nickel allergy in the European general population are approximately 8% to 19% in adults and 8% to 10% in children and adolescents, with a strong female predominance. Well-known consumer items such as jewellery and metal in clothing are still the main causes of nickel allergy and dermatitis, although a wide range of items for both private and occupational use may cause dermatitis. Allergic nickel dermatitis may be localized to the nickel exposure site, be more widespread, or present as hand eczema. Today, efficient methods for exposure quantification exist, and new insights regarding associated risk factors and immunological mechanisms underlying the disease have been obtained. Nevertheless, questions remain in relation to the pathogenesis, the persistent high prevalence, and the treatment of severe cases., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Fragrance contact allergy is common, but few studies on quality of life (QoL) in affected patients exist. Recently, the disease-specific Fragrance Quality of Life Index (FQLI) was developed., Objectives: To characterize QoL in European dermatitis patients with fragrance contact allergy at the time of diagnosis., Methods: This was a cross-sectional study, in which 2011 Danish, British, Spanish and German adult consecutive dermatitis patients were invited to complete a questionnaire on self-reported disease severity, the Dermatology Life Quality Index (DLQI), and the FQLI immediately prior to being patch tested., Results: One thousand seven hundred and fifty-eight patients responded, and 259 (14.7%; country range 11.7%-18.5%) were fragrance-positive. Among these, the total (SD) DLQI score was 6.2 (5.6) and the total (SD) FQLI score was 60 (25), with both estimates being comparable to those in fragrance-negative patients. Adjusting the total FQLI score for age, sex and self-rated disease severity showed a higher (ie, worse) score in fragrance-positive patients (3.6-point increase; 95% confidence interval: 0.30-6.8 points; P = 0.03). Specifically, contact allergy to oxidized linalool was associated with greater impairment in QoL., Conclusions: QoL in patients with fragrance contact allergy is impaired at a level comparable to that in other patch tested dermatitis patients, at the time of diagnosis, across several European countries., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: The purpose was to highlight recent findings especially concerning new and old allergens, trends, diagnosis and causes of contact allergy., Recent Findings: Nickel is still the most frequent cause of contact allergy in women and piercings remain an important risk factor. Countries with a long history of regulation of contact allergens have the lowest level of contact allergy to nickel and chromium in Europe. Among the most frequent causes of fragrance contact allergy is terpenes, which are oxidized such as limonene, linalool and in some countries: geraniol. Methylisothiazolinone is still causing considerable problems due to hidden exposures. Acrylates are emerging allergens and 2-hydroxyethyl methacrylate has been included in the 2019 update of the baseline series, as many new cases are seen due to long-lasting nail polish based on acrylates and glue (isobornyl acrylate) in insulin pumps. More than 10 new allergens have been described, which need to be considered in diagnosing contact allergy., Summary: Allergic contact dermatitis is a frequent problem, it also constitutes a challenge to diagnose due to many potential contact allergens. The main culprit allergens remain the same, new significant causes are found especially within acrylates.

Background: There is an ongoing discussion on whether routinely patch testing with p-phenylenediamine (PPD) 1.0% pet. is safe, owing to the risk of patch test sensitization. Late-appearing patch test reactions may reflect patch test sensitization, but may also be attributable to a low degree of pre-existing sensitization., Objectives: To follow the positive patch test reactions to PPD and its salt PPD dihydrochloride (PPD-DHC) in order to characterize reaction patterns concerning time and dose in PPD-sensitized individuals., Methods: Volunteers with previous reactions to PPD 1.0% were included and patch tested with PPD and PPD-DHC in equimolar dilution series. There were then seven follow-up visits over a period of 28 days., Results: Twenty-six volunteers completed the study, of whom 23 of 26 (88%) reacted to PPD 1.0%, and 69% reacted to PPD 0.32%. Altogether, 42% and 27% reacted to the corresponding equimolar concentrations of PPD-DHC. After day 7, no new reactions were observed to any concentration tested, either of PPD or of PPD-DHC., Conclusion: No late-appearing reactions to PPD or PPD-DHC were observed at any dose. There is a risk of missing contact allergy when the dose is decreased., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)