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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: 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: 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: Exposure to metalworking fluids (MWFs) is a well-known cause of occupational contact dermatitis., Objectives: We aimed to (1) determine the amount of nickel, chromium, and cobalt in large samples of used and unused MWFs collected from metalworking plants in Denmark, and (2) evaluate a handheld x-ray fluorescence (XRF) device as a screening instrument for metals in MWFs., Methods: A handheld XRF device was used to screen for metals in MWFs. All samples were also analyzed for concentrations of nickel, chromium, and cobalt using graphite furnace atomic absorption spectroscopy (GFAAS)., Results: GFAAS analysis showed that 13 of 80 samples (16.3%) contained >1 mg/kg (ppm) nickel (range: 6.4-17.7 mg/kg), 3 of 80 (3.8%) contained >1 (range: 1.4-3.1) mg/kg chromium, and 1 of 80 (1.3%) contained 1.3 mg/kg cobalt. XRF-screening detected nickel in eight samples (range: 2.5-15.5 mg/kg), but only one sample with 3.0 (±0.5) mg/kg was found subsequently to contain 9.9 (0.02) mg/kg nickel by GFAAS. Although no chromium was found by XRF analysis, cobalt was found in two samples with 6 (±1.5) mg/kg and 5 (±1.5) mg/kg, subsequently found to contain 0.1 (±0.01) mg/kg and 0.08 (±0.01) mg/kg by GFAAS. Similar concentrations of nickel were found in used (N = 6, range: 6.4-17.7 mg/kg) and unused MWFs (N = 7, range: 9.1-17.3 mg/kg)., Conclusion: Considerable levels of nickel, chromium, and cobalt were found in some used and unused MWFs indicating that these might represent a source of metal allergy. The XRF device is a poor screening test for these metals in MWFs., (© 2020 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: Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown., Objectives: To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this., Methods: The immune responses to nickel, 2,4-dinitrofluorobenzene (DNFB), cinnamal and p-phenylenediamine were assessed in ft/ft and wild-type (WT) mice. The amounts of nickel in the skin of ft/ft and WT mice were determined 20 hours after nickel exposure. The effect of blocking either the interleukin (IL)-17A pathway or the IL-1 pathway on the response to nickel in ft/ft mice was evaluated., Results: Increased responsiveness to nickel, DNFB and cinnamal was observed in ft/ft mice as compared with controls. A reduced amount of nickel was found in the skin of ft/ft mice as compared with WT mice, suggesting increased nickel absorption by the skin of ft/ft mice. Blocking either the IL-17A pathway or the IL-1 pathway reduced nickel responsiveness in ft/ft mice., Conclusions: These findings suggest that the increased nickel responsiveness associated with epidermal filaggrin deficiency is mediated by a combination of increased nickel penetration and the steady-state inflammation found in the skin of filaggrin-deficient mice., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Knowledge about the skin deposition and penetration of nickel into the stratum corneum (SC) after short contact with metallic items is limited., Objective: To quantify nickel skin deposition and penetration into the SC after short contact with metallic nickel., Methods: Sixteen nickel-allergic participants and 10 controls were exposed to 3 pure nickel discs and 1 aluminium disc on each volar forearm for 3 × 10 minutes. Before exposure, 1 forearm was irritated with 0.5% sodium lauryl sulfate under 24-hour occlusion. Immediately, as well as 24 and 72 hours after metallic disc exposure, outer SC layers were removed with adhesive tapes and the nickel content was measured., Results: Nickel deposition and SC penetration capable of eliciting allergic nickel dermatitis were found immediately and after 24 hours. Significantly higher nickel amounts were found on normal skin and in the SC of nickel-allergic participants than in controls both immediately and after 24 hours, and on irritated skin immediately after exposure., Conclusions: Nickel deposition and SC penetration is considerable after nickel skin exposure of 3 × 10 minutes. Combined with the allergic responses resulting from the same exposures reported previously, this study highlights that short skin exposure to nickel-releasing items may cause allergic nickel dermatitis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nickel contact allergy remains a problem in EU countries, despite the EU Nickel Directive. To study the prevalence of nickel allergy in EU countries following the implementation of the EU Nickel Directive, we performed a systematic search in PubMed for studies that examined the prevalence of nickel allergy in EU countries published during 2005-2016. We identified 46 studies: 10 in the general population and 36 in patch tested dermatitis patients. A significantly lower prevalence of nickel allergy after than before the implementation of the EU Nickel Directive was found in women aged 18-35 years (11.4% versus 19.8%) (p = 0.02), in female dermatitis patients aged ≤17 years (14.3% versus 29.2%) (p < 0.0001), and in dermatitis patients aged 18-30 years (women: 20.2% versus 36.6%) (p < 0.0001) (men: 4.9% versus 6.6%) (p < 0.0001). Overall, the prevalence was higher in southern than in northern EU countries, and generally remained high, affecting 8-18% of the general population. A consistent pattern of decreasing prevalence of nickel allergy in some EU countries was observed, although the prevalence among young women remains high. Steps should be taken for better prevention of nickel allergy in EU countries., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nickel in metallic items has been regulated in Denmark since 1990; however, 10% of young Danish women are still sensitized to nickel. There is a need for continuous surveillance of the effect of regulation., Objectives: To identify current self-reported metallic exposures leading to dermatitis in nickel-allergic patients, and the minimum contact time needed for dermatitis to occur., Methods: A questionnaire was sent to all patients who reacted positively to nickel sulfate 5% pet. within the last 5 years at the Department of Dermatology and Allergy, Gentofte Hospital., Results: The response rate was 63.2%. Earrings were the foremost cause of dermatitis after the EU Nickel Directive had been implemented, followed by other jewellery, buttons on clothing, belt buckles, and wrist watches. Dermatitis reactions within 10 min of contact were reported by 21.4% of patients, and dermatitis reactions within 30 min of contact were reported by 30.7% of patients., Conclusions: Nickel exposures that led to the implementation of a nickel regulation seem to persist. The durations of contact with metallic items to fall under the current REACH regulation of nickel correspond well with the results of this study., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several studies have shown nickel and cobalt release from jewellery by using spot tests, but the metal composition of jewellery is largely unknown., Objectives: To evaluate the metal composition of a large worldwide sample of mainly inexpensive jewellery items, and investigate the release of nickel, cobalt and lead from a subsample by using EN 1811:1998-required methods., Methods: A total of 956 metallic jewellery components were examined with X-ray fluorescence spectroscopy. A subsample of 96 jewellery items purchased in the United States were investigated for nickel, cobalt and lead release by the use of artificial sweat immersion and plasma optical emission spectroscopy., Results: Eighteen elements were detected. The 10 most frequently occurring were, in order of frequency, copper, iron, zinc, nickel, silver, chromium, tin, manganese, lead, and cobalt. Release of nickel was noted from 79 of the 96 US samples (0.01-98 µg/cm(2) /week), release of cobalt from 35 samples (0.02-0.5 µg/cm(2) /week), and release of lead from 37 samples (0.03-2718 µg/cm(2) /week)., Conclusions: We present here a comprehensive list of the most frequently encountered metals in jewellery and fashion accessories. Different allergenic and non-allergenic metals are utilized. We also report the frequent release of nickel, cobalt and lead from these objects, despite legislative restrictions., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The pathogenesis of total joint replacement failure is multifactorial. One hypothesis suggests that corrosion and wear of alloys result in metal ion release, which may then cause sensitization and even implant failure, owing to the acquired immune reactivity., Objectives: To assess cobalt, nickel and chromium(VI) release from, and the metal composition of, failed metal-on-ethylene total hip replacements., Materials/methods: Implant components from 52 revision cases were evaluated with spot tests for free nickel, cobalt, and chromium (VI) ions. Implant composition was determined with X-ray fluorescence spectroscopy, and information on the reason for revision and complications in relation to surgery was collected from the medical charts when possible (72%). For 10 implants, corrosion was further characterized with scanning electron microscopy., Results: We detected cobalt release from three of 38 removed femoral heads and from one of 24 femoral stems. Nickel release was detected from one of 24 femoral stems. No chromium(VI) release was detected., Conclusions: We found that cobalt and nickel were released from some failed total hip arthroplasties, and corrosion was frequently observed. Metal ions and particles corroded from metal-on-polyethylene may play a role in the complex aetiopathology of implant failure., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nickel is the most common allergen detected by patch testing in children. There is an increasing number of cases in children who have not had exposure to piercing. Although the clinical relevance of nickel patch test reactions in children is sometimes uncertain, continued vigilance to identify new sources of nickel exposure in this age group is important. Recent case reports have described allergic nickel contact dermatitis in children following exposure to toys, but the magnitude of this problem is unknown., Objective: The aim of this study was to evaluate nickel and cobalt release from children's toys., Methods: We purchased 212 toys in 18 different retail and online stores in the United States and Denmark. Nickel and cobalt release was tested using the dimethylglyoxime and cobalt screening spot tests., Results: A total of 73 toys (34.4%) released nickel, and none released cobalt., Conclusions: Toys are a commonly overlooked source of nickel exposure and sensitization. Therefore, dermatologists, allergists, and pediatricians should consider the role of toys in their evaluation of children with dermatitis, and the parents of children with positive nickel patch test reactions should be told that toys may release nickel and be a potential chemical source in the manifestation of allergic contact dermatitis.

Background: Several attempts to establish a model in mice that reflects nickel allergy in humans have been made. Most models use intradermal injection of nickel in combination with adjuvant to induce nickel allergy. However, such models poorly reflect induction of nickel allergy following long-lasting epicutaneous exposure to nickel., Objective: To develop a mouse model reflecting nickel allergy in humans induced by epicutaneous exposure to nickel, and to investigate the mechanisms involved in such allergic responses., Methods: Mice were exposed to NiCl2 on the dorsal side of the ears. Inflammation was evaluated by the swelling and cell infiltration of the ears. T cell responses were determined as numbers of CD4+ and CD8+ T cells in the draining lymph nodes. Localization of nickel was examined by dimethylglyoxime staining., Results: Epicutaneous exposure to nickel results in prolonged localization of nickel in the epidermis, and induces nickel allergy in mice. The allergic response to nickel following epicutaneous exposure is MyD88-dependent and interleukin (IL)-1 receptor-dependent, but independent of toll-like receptor (TLR)-4., Conclusion: This new model for nickel allergy that reflects epicutaneous exposure to nickel in humans shows that nickel allergy is dependent on MyD88 and IL-1 receptor signalling, but independent of TLR4., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults., Objectives: To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers., Method: Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test (ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups., Results: No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers., Conclusions: On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: We are widely exposed to metal allergens in our daily doings. As exposures constantly changes because of fashion trends and technological developments, there is a need for a continuous update of patch testers. An overview of consumer metal exposure studies that have been published in 2012 and 2013 is provided as well as lists of common metal exposures., Recent Findings: Nickel release in concentrations that cause nickel allergy and contact dermatitis is seen from laptop computers. Cobalt is found in leather as a dye and may cause chronic dermatitis. Chromium is used as a dye and for tanning in leather items and is found in nearly all shoes and released from a high proportion., Summary: New consumer items should continuously be considered and investigated for metal release when patients with positive patch test results to metal allergens are evaluated.

Background: Nickel-plated steel coins have recently been introduced in the United Kingdom., Objectives: To compare the performance and allergy risk of the new nickel-plated coins (five and ten pence) with those of the cupro-nickel coins being replaced., Materials and Methods: Coin handling studies with assessment of skin exposure and metal release in artificial sweat were performed. Six volunteers participated., Results: The amount of nickel deposited onto skin during the handling of nickel-plated coins for 1 hr was 7.5 µg/cm(2) , four times higher than that from cupro-nickel coins. The nickel content in the oxidized surface of nickel-plated coins was higher, explaining the higher skin dose. Initial nickel release rates were 10-27 times higher than 1-week rates, emphasizing that brief and repeated contact results in significant nickel exposure., Conclusions: Nickel-plated coins deposit higher levels of nickel onto skin than cupro-nickel coins, and hence pose an increased allergy risk. One-week release in artificial sweat is not suitable for determining the risk of handling items with high nickel release that come into short, repeated contact with the skin. The nickel skin dose is recommended for risk assessment. UK citizens are now, because of this change in coinage, unnecessarily exposed to higher levels of nickel on the skin. This is of public health concern., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nickel is widely used in coins; nickel may cause contact allergy and allergic contact dermatitis in those who handle them., Objectives: To investigate alloy use, coin composition and nickel and cobalt release for a worldwide selection of currently circulating coins., Materials and Methods: Eight hundred and fifty coins of 361 different denominations or issues from 52 countries were collected and analysed with X-ray fluorescence spectrometry and nickel and cobalt spot tests., Results: Copper-nickel was the most frequently identified coin alloy, being observed in 100 denominations (28%), followed by aluminium-bronze (62, 17%). In total, 239 denominations released nickel (28%). Coins from Bolivia, Brazil and Costa Rica did not release nickel. Fewer than one-third of the denominations or issues from China, India, the euro area and Indonesia released nickel. In the United States, the Russian Federation, Japan, and Mexico, one-third or more of the denominations released nickel., Conclusions: This worldwide selection of circulating coins covered countries with 75% of the world population, and shows that the majority of the world population lives in countries where coins release nickel. Pertinently, ∼ 40% of circulating coin denominations do not release nickel., (© 2012 John Wiley & Sons A/S.)

Nickel is used in coins because the metal has beneficial properties, including price, colour, weight, and corrosion resistance, and also because it is easy to stamp. It has often been claimed that the duration of skin contact with coins is too short to cause nickel release and dermatitis. However, it is well known by dermatologists specialized in occupational skin diseases, and by their nickel-allergic patients, that hand eczema in cashiers and other professionals who handle coins may be caused or aggravated by nickel release from coins. In this review, we present evidence from past studies showing that nickel-containing coins can indeed pose a risk for those who handle them. For protection of the health of consumers, cashiers, and other workers who handle coins, it is suggested that coins without nickel release should be used as a substitute for the high nickel-releasing coins currently in widespread use. The key risk factor in this situation is the ability of metal alloys in coins to release nickel and contaminate the skin after repeated contact from coin handling., (© 2012 John Wiley & Sons A/S.)

Background: Nickel and cobalt are common causes of metal allergy., Objective: The objective of this study was to investigate nickel and cobalt exposure in belt buckles by testing 701 belts purchased in China and the United States and to consider the prevalence of nickel allergy and its relevance among Chinese patients., Methods: Seven hundred one belt buckles purchased in China and the United States were tested for nickel and cobalt release. Six hundred thirty-one Chinese patients with suspected allergic contact dermatitis were patch tested and interviewed to determine clinical relevance of results. The Chinese and American literature was reviewed to investigate trends in nickel prevalence over the past decades., Results: Sixty percent (n = 219) of belts purchased in China (n = 365) released nickel, and 0.5% (n = 2) released cobalt; 55.7% (n = 187) in the United States (n = 336) released nickel, and 0.9% (n = 3) released cobalt. Belt dermatitis was a significant clinical finding in 34.8% of Chinese nickel-allergic patients. Literature review suggests increasing nickel allergy prevalence in the United States and China., Conclusions: Metallic belt buckles are an important source of nickel exposure to consumers. Belts from lowest socioeconomic vendors were more likely to release nickel. Belts with silver color and dark metallic color were more likely to release nickel and cobalt, respectively. Clinical findings show belt dermatitis in China to be a problem.

Background: Despite the political intention to limit nickel allergy and dermatitis in Europeans, nickel allergy remains frequent. There are several explanations for the persistence of nickel allergy and dermatitis, including the increasing use of mobile phones. Before regulation of nickel release from mobile phones, we showed that eight (19.5%) of 41 mobile phones marketed in Denmark between 2003 and 2007 released nickel in concentrations that may result in nickel allergy and dermatitis. In 2009, the EU Nickel Directive was revised to include nickel-releasing mobile phones., Objectives: To investigate the proportion of mobile phones sold in Denmark that release nickel after regulation., Methods: Metallic parts from 50 randomly selected mobile phones currently for sale in Denmark were tested for nickel release by use of the dimethylglyoxime (DMG)-nickel spot test., Results: Nine (18%) phones showed at least one positive DMG test reaction and two phones had more than one DMG test-positive spot., Conclusions: Apparently, the proportion of mobile phones with significant nickel release remains unchanged, despite the 2009 revision of the EU Nickel Directive. We encourage manufacturers to measure nickel release from metallic components used in the assembly of mobile phones to ensure safe products., (© 2011 John Wiley & Sons A/S.)

Introduction: Nickel and cobalt allergy remain frequent in dermatitis patients. It is important to determine possible nickel and cobalt exposures at work as these may offer important information to regulators and physicians who perform patch testing. Clinical relevance of metal exposure is usually assessed by the treating physician via the medical history and by presentation of allergic contact dermatitis., Objectives: To screen unused non-powered hand-held work tools for nickel and cobalt release by using colorimetric spot tests., Materials & Methods: A random selection of 200 non-powered hand-held work tools for sale in 2 retailers of home improvement and construction products were analyzed qualitatively for metal release using the colorimetric nickel and cobalt spot tests., Results: Nickel release was identified from 5% of 200 work tools using the dimethylglyoxime (DMG) test. In 8 of 10, positive results were located to the metal ring that acts like a cuff and is located at the end of the grip. The positive DMG test results were not related to specific categories of work tools. The cobalt spot test gave no positive test reactions., Conclusions: It appears that the proportion of work tools that release nickel, in amounts that may result in allergic nickel dermatitis, has decreased markedly, when results were compared with a Swedish study performed more than a decade ago. No cobalt release was detected but it should be underscored that hard-metal tools were not examined. Other sources of cobalt may explain the relatively high levels of cobalt allergy in dermatitis patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In July 2001, the EU Nickel Directive came into full force to protect European citizens against nickel allergy and dermatitis. Prior to this intervention, Northern European governments had already begun to regulate consumer nickel exposure. According to part 2 of the EU Nickel Directive and the Danish nickel regulation, consumer items intended to be in direct and prolonged contact with the skin were not allowed to release more than 0.5 µg nickel/cm2/week. It was considered unlikely that nickel allergy would disappear altogether as a proportion of individuals reacted below the level defined by the EU Nickel Directive. Despite this, the EU Nickel Directive part 2 was expected to work as an operational limit that would sufficiently protect European consumers against nickel allergy and dermatitis. This review presents the accumulation of epidemiological studies that evaluated the possible effect of this major public health intervention. Also, it evaluates recent exposure assessment studies that have been performed using the dimethyl glyoxime test. It is concluded that the EU Nickel Directive has started to change the epidemiology of nickel allergy in Europe but it should be revisited to better protect consumers and workers since nickel allergy and dermatitis remain very frequent., (© 2011 John Wiley & Sons A/S.)

Background: It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum., Objectives: To investigate whether subjects with filaggrin null mutations report nickel dermatitis at an earlier age than wild-type individuals, and to analyse whether null mutation carriers have stronger patch test reactivity to nickel sulfate than do wild-type individuals., Materials: A total of 3471 Danes (18-69 years of age) answered a questionnaire about general health, and underwent patch testing and filaggrin genotyping., Results: The mean number of years at risk of developing nickel dermatitis was significantly lower for the filaggrin null genotype than for the wild-type genotype when ear piercing status was considered. In positive patch test readings, the proportion of null mutants increased with increasing reaction strength., Conclusions: Filaggrin null mutations may lower the age of onset of nickel dermatitis. The hypothesis that ear piercings obscure the effect of filaggrin null mutations on the development of nickel allergy in statistical analyses was supported. An association between the null genotype and increased nickel sensitivity was indicated by patch test reading and questionnaire data., (© 2010 John Wiley & Sons A/S.)

Background: EU legislation has reduced the epidemic of nickel contact allergy affecting the consumer, and shifted the focus towards occupational exposure. The acid wipe sampling technique was developed to quantitatively determine skin exposure to metals., Objectives: To assess the clinical usefulness of the acid wipe sampling technique as part of the diagnostic investigation for occupational nickel allergy-associated hand dermatitis., Patients and Methods: Six patients with vesicular dermatitis on the hands were included. Acid wipe sampling of skin and patch testing with a nickel sulfate dilution series were performed., Results: Nickel was detected in all samples from the hands. In all patients, the nickel content on the hands was higher than on the non-exposed control area., Conclusions: Occupational exposure to nickel-releasing items raised the nickel content on exposed skin as compared with a non-exposed control site. Nickel-reducing measures led to complete symptom relief in all cases. In cases of a positive nickel patch test reaction and hand eczema, patients should perform the dimethylglyoxime (DMG) test on metallic items at home and at work. The acid wipe sampling technique is useful for the diagnosis of occupational hand eczema following screening with the inexpensive DMG test., (© 2010 John Wiley & Sons A/S.)

Introduction: Nickel allergy is prevalent as assessed by epidemiological studies., Objectives: In an attempt to further identify and characterize sources that may result in nickel allergy and dermatitis, we analysed items identified by nickel-allergic dermatitis patients as causative of nickel dermatitis by using the dimethylglyoxime (DMG) test., Materials and Methods: Dermatitis patients with nickel allergy of current relevance were identified over a 2-year period in a tertiary referral patch test centre. When possible, their work tools and personal items were examined with the DMG test., Results: Among 95 nickel-allergic dermatitis patients, 70 (73.7%) had metallic items investigated for nickel release. A total of 151 items were investigated, and 66 (43.7%) gave positive DMG test reactions. Objects were nearly all purchased or acquired after the introduction of the EU Nickel Directive. Only one object had been inherited, and only two objects had been purchased outside of Denmark., Conclusions: DMG testing is valuable as a screening test for nickel release and should be used to identify relevant exposures in nickel-allergic patients. Mainly consumer items, but also work tools used in an occupational setting, released nickel in dermatitis patients. This study confirmed 'risk items' from previous studies, including mobile phones.

Background: The accuracy of the dimethylglyoxime (DMG) nickel spot test has been questioned because of false negative and positive test reactions. The EN 1811, a European standard reference method developed by the European Committee for Standardization (CEN), is fine-tuned to estimate nickel release around the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test., Objectives: To evaluate the sensitivity and specificity of the DMG test., Methods: DMG spot testing, chemical analysis according to the EN 1811 reference method, and X-ray fluorescence spectroscopy (XRF) were performed concomitantly on 96 metallic components from earrings recently purchased in San Francisco., Results: The sensitivity of the DMG test was 59.3% and the specificity was 97.5% based on DMG-test results and nickel release concentrations determined by the EN 1811 reference method., Conclusions: The DMG test has a high specificity but a modest sensitivity. It may serve well for screening purposes. Past exposure studies may have underestimated nickel release from consumer items.

Background: China and Thailand produce large amounts of jewellery that are sold domestically and abroad., Objective: To identify nickel release and metal content in earrings purchased in China and Thailand., Methods: A total of 557 earrings were randomly purchased from vendors in 11 markets located in Beijing, Chengdu, Bangkok, Patong Beach, and Hat Yai. Earrings were subjected to dimethylglyoxime (DMG) tests and 26 of the DMG negative earrings were further evaluated qualitatively for major and minor metal content using X-ray fluorescence spectrometry., Results: A total of 314 Chinese earrings (31.5%) and 243 Thai earrings (29.2%) were DMG test positive. Three (11.5%) of 29 DMG negative earrings contained nickel as a major component; 7 (26.9%) of 29 DMG negative earrings contained nickel as a minor component., Discussion: Excessive nickel release was frequent. This may contribute to the high prevalence of nickel allergy in both countries. Increased public education together with the adoption of a regulatory intervention in Thailand may be warranted. In China, enforcement of the 2002 Chinese National Standard GB 11887 may assist in reducing sensitization. These initiatives may eventually result in decreased morbidity among the Chinese and Thai citizens, but can potentially benefit recipient countries of these important earring producing countries.

There is evidence that stimulants such as alcohol and tobacco have an effect on the immune system, but little is known about how these lifestyle factors affect the prevalence of contact sensitization. This study investigated whether smoking and alcohol consumption were associated with contact sensitization and nickel sensitization. A random sample of adults (n=3460) from the general population of Copenhagen was invited to participate in a general health examination including patch-testing. Alcohol consumption was not associated with nickel sensitization, whereas a significant trend (p<0.05) was identified between smoking status and nickel sensitization in an adjusted model; i.e. nickel sensitization was higher among both previous smokers (odds ratio (OR) = 1.19; confidence interval (CI) = 0.81-1.76), current light smokers (OR=1.50; CI=0.94-2.37) and current heavy smokers (OR=1.56; CI = 0.87-2.80) compared with never smokers. This study confirmed that smoking is associated with nickel sensitization, but rejected an association with alcohol consumption.

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. [ABSTRACT FROM AUTHOR]

Background: Exposure to nickel releasing ear piercing jewellery may explain the persistently high prevalence of nickel allergy in Europe. While nickel release from earrings is regulated, field studies show that the regulation is not always respected. More knowledge is needed regarding the risk of piercing exposure including suitable screening methods. Objective: To examine the proportion of earrings on the Danish market that release more nickel than allowed, and to validate the use of the dimethylglyoxime (DMG) test as a screening tool. Methods: A total of 304 earrings were purchased and tested with the DMG test and X-ray fluorescence spectrometry. The level of nickel release was quantified in a selected subsample of 100 earrings by the European reference test EN 1811. The DMG spot test was validated against EN 1811 at different thresholds. Results: Excessive nickel release according to the European regulation was found in 45 (14.8%) tested earrings. The sensitivity of the DMG test decreased with reduced levels of nickel release (sensitivity of 45.2% at =0.2 µg/cm²/week vs 61.1% at >0.5 µg/cm²/week). Conclusion: Excessive nickel release is common in earrings on the Danish market. Because of low sensitivity, the DMG test has limited use in screening of earrings for research but may still be used clinically. [ABSTRACT FROM AUTHOR]