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.

Contact allergens in African countries: A review of published patch test studies.

Only few studies on contact allergy in African countries have been published. The aim of the present study was to provide an overview of the most common contact allergens identified by the use of patch tests in African countries based on a review of the existing literature. A total of twenty-four publications from eight African countries were initially identified by search in PubMed. The abstracts and method sections were screened, and 15 studies in which patch tests were actually used to identify the allergen causing the allergic contact dermatitis (ACD) were finally selected. Nickel, cobalt, chromium, fragrance mix and p-tert-butylphenol-formaldehyde resin were the dominating contact allergens responsible for 40%-90% of the positive patch test reactions. This study indicates that a targeted effort directed towards prevention, avoidance and regulation of reliably identified contact allergens could reduce the disease burden of ACD considerable in some African countries.

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

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

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

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

Occupational contact dermatitis among young people in Denmark - A survey of causes and long-term consequences.

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.

Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-µg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

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.

Incidence rates of occupational contact dermatitis in Denmark between 2007 and 2018: A population-based study.

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.

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.

The epidemic of contact allergy to methylisothiazolinone-An analysis of Danish consecutive patients patch tested between 2005 and 2019.

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.

Degree of employment, sick leave, and costs following notification of occupational contact dermatitis-A register-based study.

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.

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.

Nickel deposition and penetration into the stratum corneum after short metallic nickel contact: An experimental study.

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.

Prevalence of nickel allergy in Europe following the EU Nickel Directive - a review.

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.