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.

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.

Automated Quantum Dots Purification via Solid Phase Extraction.

The separation of colloidal nanocrystals from their original synthesis medium is an essential process step towards their application, however, the costs on a preparative scale are still a constraint. A new combination of approaches for the purification of hydrophobic Quantum Dots is presented, resulting in an efficient scalable process in regard to time and solvent consumption, using common laboratory equipment and low-cost materials. The procedure is based on a combination of solvent-induced adhesion and solid phase extraction. The platform allows the transition from manual handling towards automation, yielding an overall purification performance similar to one conventional batch precipitation/centrifugation step, which was investigated by thermogravimetry and gas chromatography. The distinct miscibility gaps between surfactants used as nanoparticle capping agents, original and extraction medium are clarified by their phase diagrams, which confirmed the outcome of the flow chemistry process. Furthermore, the solubility behavior of the Quantum Dots is put into context with the Hansen solubility parameters framework to reasonably decide upon appropriate solvent types.

Evaluation of the secondary and tertiary prevention strategies against occupational contact dermatitis in Germany: A systematic review.

In Germany, a stepwise multidisciplinary approach has been established to prevent occupational skin diseases (OSDs), primarily occupational contact dermatitis. This review aims to perform a systematic evaluation of the short- and long-term effects of the German secondary and tertiary individual prevention programmes (SIP and TIP, respectively) for OSDs. Primary outcomes were continuation of employment, severity of hand dermatitis, and quality of life (QoL). The PubMed and Embase databases were searched for studies reporting the effects of the SIP and TIP. A total of 19 studies encompassing 5527 patients with OSDs were included: 11 studies evaluated the SIP and 8 evaluated the TIP. Following the SIP, approximately 70% to 90% and 60% to 70% of patients remained in their occupation after 1 and 5 years, respectively. At 3 years after the TIP, 82.7% of patients remained in their occupation and exhibited a significant decrease in hand dermatitis severity, as well as an increase in QoL. Most of these studies were uncontrolled and the interventions, outcomes, and measurement instruments used were heterogeneous. The SIP and TIP lead to decreased disease severity, improved QoL, and enabled most patients to continue working in their chosen professions. Implementing a similar multidisciplinary approach across Europe may be beneficial.

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.

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.

Decrease of contact allergy to hydroxyisohexyl 3-cyclohexene carboxaldehyde in Europe prior to its ban and diagnostic value.

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.

The stratum corneum transcriptome in atopic dermatitis can be assessed by tape stripping.

BACKGROUND: Skin biopsies represent a gold standard in skin immunology and pathology but can cause pain and induce scarring. Non-invasive techniques will facilitate study recruitment of e.g. patients with paediatric atopic dermatitis (AD), hand eczema or facial dermatitis. OBJECTIVE: By RNA sequencing, we examined whether the stratum corneum transcriptome in AD skin can be assessed by tape stripping, as compared to the epidermal transcriptome of AD in skin biopsies. To make the procedure clinically relevant tape strips were stored and shipped at room temperature for up to 3 days. METHODS: Nine adult Caucasian AD patients and three healthy volunteers were included. Tape samples were collected from non-lesional and lesional skin. Biopsies were collected from lesional skin and were split into epidermis and dermis. Total RNA was extracted, and shotgun sequencing was performed. RESULTS: Shotgun sequencing could be performed on skin cells obtained from two consecutive tape strips which had been stored and shipped at room temperature for up to three days. The most prominent differences between the tape strip and biopsy derived transcriptome were due to structural genes, while established molecular markers of AD, including CCL17, CCL22, IL17A and S100A7-S100A9, were also identified in tape strip samples. Furthermore, the tape strip derived transcriptome showed promise in also analysing the skin microbiome. CONCLUSION: Our study shows that the stratum corneum (SC) transcriptome of AD can be assessed by tape stripping the skin, supporting that this method may be central in future skin biomarker research. NCBI GEO data accession: GSE160501.

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.

Peritoneal dialysis throughout pregnancy with successful outcome: A case report.

We present the case of a 28-year-old woman who was para 1, with end-stage renal failure secondary to reflux nephritis. She conceived after two years on peritoneal dialysis. She successfully continued this throughout pregnancy, although her antenatal course was complicated by an episode of peritonitis. Induction at 34 weeks resulted in a vaginal birth of a live boy. Her postnatal course was uncomplicated. We reviewed the literature regarding peritoneal dialysis in pregnancy. A recent systematic review identified 14 cases. When the outcomes of these women were compared with those receiving haemodialysis in pregnancy, there was a significantly higher proportion of small for gestational age fetuses, but other parameters were comparable. Two cases of peritonitis complicating peritoneal dialysis in pregnancy have been reported, both successfully treated. We conclude that peritoneal dialysis may be continued in pregnancy with successful maternal and fetal outcome, particularly in women with some residual renal function.

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.

Nickel allergy in a Danish population 25 years after the first nickel regulation.

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.