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

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

Chromium and cobalt release from metallic earrings from the Danish market.

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/cm2 /week) and cobalt release from 29/100 (median concentration = -0.06 µg/cm2 /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.

Aluminium contact allergy without vaccination granulomas: A systematic review and meta-analysis.

Aluminium contact allergy is mainly seen as granulomas following immunization with aluminium-adsorbed vaccines and contact allergy following epicutaneous exposure may be overlooked. To investigate the prevalence of aluminium allergy confirmed by patch testing, with no association with vaccination granulomas, and explore whether epicutaneous exposure to aluminium can contribute to allergic contact dermatitis. Two authors independently searched PubMed and MEDLINE (OVID) for case studies on contact allergy to aluminium proven by patch testing. Age-stratified meta-analyses to calculate the pooled prevalence were performed. Twenty-five studies describing a total of 73 cases were included in the review. Seven studies were suitable for meta-analyses. The prevalence of aluminium contact allergy was 5.61% (95% confidence interval [CI] 0.12%-11.08%) for children and 0.36% (95% CI 0.04%-0.67%) for adults. The studies described a variety of epicutaneous exposures, where metallic aluminium, topical medicaments, and deodorants were the main sources. Aluminium sensitization without a known exposure source was described in 10 of the 25 articles. The prevalence of aluminium contact allergy in the general public may be higher than expected and not solely related to vaccination granulomas. However, the clinical relevance is rare if not related to granulomas.

Nickel release from metallic earrings: A survey of the Danish market and validation of the nickel spot test.

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.

Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment.

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.