Nickel Sensitivity Research Articles

Epidemiology of patch tested patients with permanent tattoos-A comparative analysis of 9693 IVDK patients (2020-2022).

Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers. To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant. Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53]). The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups.

Associations between tobacco smoking status and patch test results-A cross-sectional pilot study from the Information Network of Departments of Dermatology (IVDK).

Earlier studies suggested a potential association between tobacco smoking and nickel sensitization, but little is known about other contact allergens. To investigate the association of smoking status and contact sensitizations as well as subtypes of dermatitis, and to analyse the sensitization profiles of tobacco smokers. Within the Information Network of Departments of Dermatology (IVDK), we performed a cross-sectional multicentre pilot study comprising 1091 patch-tested patients from 9 departments, comparing 541 patients with a history of cigarette smoking (281 current and 260 former smokers) with 550 never-smokers. We could not confirm the previously reported association between nickel sensitization and tobacco smoking. Moreover, sensitizations to other allergens, including colophony, fragrance mix I, Myroxylon pereirae and formaldehyde, were not increased in cigarette smokers compared with never smokers. Hand dermatitis (50.6% vs. 33.6%) and occupational cause (36.2% vs. 22.5%) were significantly more frequent among cigarette smokers compared with never-smokers as shown by non-overlapping 95% confidence intervals. Although our study does not allow a firm conclusion on whether smoking status contributes to certain contact sensitizations, it confirms an association of smoking with hand dermatitis and occupational cause.

A Novel Digitized Method for the Design and Additive Manufacturing of Orthodontic Space Maintainers

Primary dentition is crucial in influencing the emergence of permanent teeth. Premature primary tooth loss can result in undesired tooth motions and space loss in the permanent dentition. Typically, fixed or removable dental appliances are adopted to maintain edentulous space until the eruption of permanent teeth. However, traditional space maintainers have limitations in terms of variability in tooth anatomy, potential allergic reactions in some individuals (i.e., nickel sensitivity), difficulties in maintaining oral hygiene, and patient acceptance. The present study introduces a fully digital framework for the design and manufacturing of customized pediatric unilateral space maintainers using generative algorithms. The proposed approach overcomes the current challenges by using a biocompatible resin material and optimizing the device’s size, design, and color. The methodology involves intraoral scanning, surface selection, and trim, generative 3D modeling, finite element analysis (FEA), and additive manufacturing (AM) through vat photopolymerization. FEA results demonstrate the device’s mechanical performance and reliability, while additive manufacturing ensures design freedom, high resolution, surface finishing, dimensional accuracy, and proper fit. The mechanical interlocking system facilitates easy and effective positioning of the device. This digital approach offers the potential for wider usage of space maintainers and can be further validated through experimental assessments and clinical studies.

Contact hypersensitivity and Demodex mite infestation in patients with rosacea: a retrospective cohort analysis

Contact hypersensitivity or Demodex mite infestation is commonly reported in patients with rosacea. However, the associations and clinical implications of these two phenomena are poorly described in the literature. This study aimed to investigate the association between clinical characteristics, contact sensitization profiles, and Demodex mite infestation in patients with rosacea. We retrospectively reviewed 189 patients diagnosed with rosacea, and categorized the patients into a rosacea-contact hypersensitivity or rosacea-non-contact hypersensitivity group. The rosaceacontact hypersensitivity group had older age (median: 45.5 vs. 37.0 years; p = 0.006), a higher frequency of itching (63.0% vs. 45.1%; p = 0.040), and a higher Demodex mite density (15.0/cm2vs. 7.0/cm2; p = 0.002) than the rosacea-non-contact hypersensitivity group. Nickel sensitization was correlated with a higher Demodex mite density, female sex, and papulopustular subtype of rosacea. Based on the multivariate regression model, a favourable clinical outcome was correlated with nickel sensitization alone (odds ratio: 2.20, 95% confidence interval: 1.01-4.81). Patients with rosacea and contact hypersensitivity showed distinctive clinical features and a higher Demodex mite density. The association between nickel sensitization, Demodex mite infestation, and treatment response may reflect the role of allergen-specific TH polarization in the pathogenesis of rosacea.

Clinical predictors of metal allergic sensitization in orthodontic patients.

This study aimed to assess the predictors of allergic sensitisation to titanium and nickel in patients undergoing orthodontic treatment. A total of 250 patients undergoing orthodontic treatment were invited to participate, and 235 were analysed (67% females). A patch test was performed using nickel sulphate, titanium, titanium dioxide, titanium oxalate, titanium nitride, and petrolatum as control. In addition, clinical signs of the oral mucosa, gingiva, tongue, lips, and allergological history were assessed. The predictors of metal allergic sensitisation in patients undergoing orthodontic treatment were adult age (OR = 2.6; 95% CI: 1.2-5.5; p = 0.016), female sex (OR = 3.0; 95% CI: 1.1-7.9; p = 0.025), exfoliative cheilitis (OR = 4.8; 95% CI: 1.9-12.4; p = 0.001), history of contact hypersensitivity (OR = 7.0; 95% CI: 1.3-35.4; p = 0.025), history of contact hypersensitivity to metals (OR = 8.3; 95% CI: 1.4-50.2; p = 0.021), and piercings (OR = 5.4; 95% CI: 2.1-13.9; p = 0.001). When predictors were analysed separately for these two metals, titanium sensitisation predictors were contact hypersensitivity to metals and piercing, whereas nickel sensitisation predictors were age and piercing. A positive patch test alone cannot draw definite conclusions regarding allergy. However, metal allergies in patients with orthodontic appliances could be considered in cases of previous contact hypersensitivity, previous reactions to metals, exfoliative cheilitis, and piercing.

Sensitization to Nickel Associates with HLA-DR53 (DRB4*01) in Implant Failure Patients; the Association is Confirmed in a DR53 Transgenic Mouse Model

Nickel sensitization is the most common cause of implant failure due to component allergy. Predictors of failure due to nickel allergy are lacking. We hypothesized that one or more MHC's more effectively present nickel (Ni2+) to sensitized T cells, and associate with implant failure.

Immunogenicity of Nickel-Further Explored.

Recent reports of the relationship between nickel, allergy and autoimmunity have been described. However, there remains a lack of information on the concordance between nickel sensitization and potency. Of note, an article by Drenovska et al. recommended a call for increased epidemiologic studies to define the prevalence of autoimmune syndromes induced by adjuvants such as nickel-containing metal implants. Accumulating reports of dermatologic manifestations following medical device implantation highlights the need for consideration regarding the potential sequelae following metal implantation. Considering the medical and the functional necessity of certain device materials, the authors agree calling for further epidemiological studies are needed to prevent metal-related autoimmunity, and additionally discover novel testing strategies.

Patch Test Positivity to Palladium: A 5-Year Retrospective Study in Triveneto Region, Italy.

The use of palladium (Pd) is increasing in metal objects after the banning of nickel in items in prolonged contact with the skin. The properties of Pd make this metal useful in various industrial fields. The aim of the study was to evaluate the prevalence of Pd sensitization in patients who underwent patch tests for suspected allergic contact dermatitis in the Triveneto region from 2013 to 2018. A total of 4816 patients with symptoms and/or signs of suspected contact allergic dermatitis were patch tested. Individual characteristics were assessed using a standardized questionnaire. The overall prevalence of Pd sensitization was 7.6% and 10.8% using PdCl2 1% or 2% petrolatum, respectively, with a higher prevalence in women (odds ratio, 2.6; 95% confidence interval, 1.9-3.7) and in 26- to 55-year-old patients. Monosensitization occurred in 1%-1.5% of the patients tested. Health care workers and technicians were more sensitized to Pd than clerks, but the data did not reach statistical significance. Palladium sensitization was high, but it was mainly associated with nickel sensitization. A possible occupational role was found for workers with potential contact with Pd-containing objects, but more data are needed to reach statistical significance.

Prevalence of Contact Allergy to Nickel: A Retrospective Chart Review.

No recent studies reporting nickel sensitivity prevalence in Canadians exist. The aim of this study was to quantify nickel sensitivity prevalence in patients at a patch test clinic in Vancouver. Retrospective chart review of 3263 patients patch tested for nickel sensitivity at our clinic in Vancouver between 2008 and 2020. In total, 24.3% (n = 792 of 3263) of patients were sensitive to nickel. Nickel sensitivity significantly increased over time from 24.3% to 27.9% from 2008 to 2020. Nickel-sensitive patients were significantly more likely to be women (P < 0.001), between the ages of 19 and 64 years (P = 0.010), and have dermatitis affecting the face (P = 0.001) and hands (P = 0.001). Nickel-sensitive patients were significantly less likely to be 65 years or older (P = 0.001) and have dermatitis affecting the legs (P = 0.002). Approximately half of nickel-sensitive reactions were new positive reactions at the second reading. Nickel sensitivity occurred in approximately one quarter of patients and significantly increased over time. Nickel-sensitive patients were more likely to be women, aged 19 to 64 years, and have dermatitis affecting the face and hands; and less likely to be 65 years or older and have dermatitis affecting the legs.

Allergic Sensitization to Nickel and Implanted Metal Devices: A Perspective.

There is continuing interest in the interrelationships between allergic sensitization to metal allergens, metal implants, and the development of adverse reactions to implanted devices. Here, we focus on sensitization to nickel (although, in practice, it is commonly not possible to distinguish between events associated with nickel and other potentially allergenic metals used in devices). The purpose of this article was to review whether exposure to nickel resulting from implanted devices is associated with the development of de novo sensitization to nickel and also whether nickel sensitization, either newly acquired or pre-existing, has a causal relationship with adverse health effects. In addressing these issues, a variety of devices, including metal-on-metal hip implants, cardiac and endovascular stents and filters, and the gynecologic implant Essure, are considered. Also addressed is the question of whether pre-operative assessment of nickel allergy (and allergy to other implant metals) is required. The conclusions reached are that (a) sensitization can potentially be acquired as the result of exposure to implants containing nickel, but is not a common occurrence; (b) sensitization to nickel and/or other metal allergens is very rarely a cause of adverse reactions to implants; and (c) routine preoperative patch testing for sensitization to nickel is unnecessary, unless there is a significant clinical history of nickel allergy.

Trend in the variation of sensitization of the European standard battery allergens over 26 years

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Epidemiological monitoring of sensitization rates to common allergens and identification of emerging allergens are needed to assess preventive measures. The aim of this study was to assess trends in the frequencies of sensitization to the different allergens in the European standard battery over a 26 year period from 1989 to 2015.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; It’s a descriptive study of the trend of sensitization to BSE allergens over a period of 26 years, at the dermato-allergology unit of occupational medicine department of Farhat Hached university hospital-Sousse (Tunisia), based on the results of patch tests of all patients who consulted the unit between 1989 and 2015.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; During the study period, 1716 patients were patch tested, 48048 patch tests were performed with 886 positive tests to at least one allergen (51.6%). Between 1989 and 2015, the number of positive patch tests has shown a significantly positive trend with an annual percentage change (APC) of 10.03% (p&amp;lt;10&lt;sup&gt;-3&lt;/sup&gt;). However, the overall frequency of sensitization to BSE allergens decreased with an APC of -0.87%, p=0.2. The APC of chromium sensitization was -2.57% (p&amp;lt;10&lt;sup&gt;-3&lt;/sup&gt;). The frequency of cobalt sensitization showed a non-significant decrease (APC=-0.28%, p=0.9). The frequency of nickel sensitization increased with an APC of +2.7%, p=0.1). Overall, there was a statistically significant growth between 1989 and 2015 in the BSE preservatives sensitization trend with an APC of +5.54% per year (p&amp;lt;10&lt;sup&gt;-3&lt;/sup&gt;). The frequency of sensitization to mix fragrances increased from 2004 to 2015, with a significantly positive trend (APC=+24.33%, p&amp;lt;10&lt;sup&gt;-3&lt;/sup&gt;).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Although the frequency of some BSE allergens sensitization tends to decrease, it remains high. Consistent preventive measures should be focused, mainly on sensitization to perfumes and preservatives used in the cosmetic industry.&lt;/p&gt;

Nickel Sensitivity in Children Due to Using Stainless Steel Crowns: A Narrative Review

Context: Stainless Steel Crowns (SSC) are stable and durable restorations and a valuable technique in repairing deciduous teeth with extensive caries. Nickel and chromium are the main composing elements of SSCs, i.e. released in the oral environment; they can cause allergic reactions, especially in nickel-sensitive children. The symptoms of these reactions include gingival edema and the loss of alveolar bone. Evidence Acquisition: The required data used in our review were searched from articles published until 2020 and collected from online databases, including Scopus, PubMed, Google Scholar, and Science Direct, using “Nickel, Allergy, and SSCs” keywords. Articles concerning SSCs and their application, nickel allergy released from crowns, and their symptoms were included in this study. After the abstract screening, we recalled relevant studies for full-text review. Results: We are exposed to nickel every day in various forms; some individuals present hypersensitivity reactions when exposed to the slightest amounts of this metal. Nickel is a base metal and among the elements used in SSCs. Nickel is released from SSCs during the corrosion process in the oral environment. Excessively released nickel ions cause chronic fatigue syndrome, sensitive lymph nodes, muscle aches, and headaches. Conclusions: The amount of nickel released from SSCs is less than the number of other sources; thus, the immunological reactions of a large percentage of the population to this excess amount of nickel ions in the bloodstream are normal and cause no severe problems.

Sensitization to Implant Components Is Associated with Joint Replacement Failure: Identification and Revision to Nonallergenic Hardware Improves Outcomes

Over 90% of one million annual US jointreplacements are highly successful. Nonetheless, 10% dopoorly owing to infection or mechanical issues. Many implant components are sensitizers, and sensitization couldalso contribute to implant failure. To determine the prevalence of implant sensitization in joint failure patients, their clinical characteristics, and implant revision outcomes. We hypothesized that sensitized patients would improve when revised with nonallergenic materials. We prospectively enrolled 105 joint failure patients referred by orthopedic surgeons who had already excluded infection or mechanical causes. Patients provided informed consent, completed a history and physical examination, patch testing to metals and bone cement, and a nickel lymphocyte proliferation test. A study coordinator was able to contact 64%of patients (n= 67) 9 to 12 months later to evaluate outcomes. A total of 59% were sensitized to an implant component: 32% to metal and 37% to bone cement. The nickel lymphocyte proliferation test was 60% sensitive and 96% specific in diagnosing nickel sensitization. Most sensitized subjects reported no or uncertain histories of reactions to a specific material. Implant sensitized patients were younger and reported previous eczema, joint itching, and implant loosening. By 9 to 12 months later, most patients with a revised implant (revised) described significant improvement (16 of 22 revised for sensitization [P= .0003] vs 9 of 13 revised without sensitization [P= .047]) compared with patients without implant revision). All revised patients with sensitization used components to which they were not sensitized. Pain (P= .001), swelling (P= .035), and instability (P= .006) were significantly reduced in the revised sensitized group. Sensitization to implant components is an important cause of unexplained joint replacement failure. Joint revisions based on sensitization information resulted in significant improvements.

An ICP-MS Study for Quantitation of Nickel and Other Inorganic Elements in Urine Samples: Correlation of Patch Test Results with Lifestyle Habits.

Nickel (Ni) is a frequently used metal in the production of many products, and Ni exposure occurs in humans through food, inhalation, and skin. Studies reported Ni as the most common allergen diagnosed in the serial patch test. The main purpose of our study was to determine the concentration of Ni and other elements in the urine samples of individuals with Ni-sensitivity and to determine the effect of lifestyle habits on these variables. This study was conducted with 388 participants; additionally, both Ni patch test and inorganic analysis (for 24 elements)method in urine with inductively coupled plasma-mass spectrometry (ICP-MS)were applied to all participants. Ninety-two (23.7%) of the participants were found to have nickel sensitivity with a mean urine concentration of 4.475 μg/g creatinine (median=4.260; SD=2.527). The urine nickel concentration was significantly different between female and male participants (p =0.001). We found a significant correlation between Ni and other metals alongside various element pairs. The mean urine Ni concentration of the individuals with a positive Ni sensitivity test result was not different from that of the participants without Ni sensitivity (4.475 vs 4.256 μg/g creatinine, respectively; p = 0.068). The high accuracy, recovery, and repeatability data obtained from the analyses indicate that this study is efficient and appropriate for the quantitative determination of nickel and other elements in urine samples. Ni-containing objects and Ni-rich foods should be of concern for individuals with hypersensitivity reactions to the element.

Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects.

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.

The effect of a low-nickel diet and nickel sensitization on gastroesophageal reflux disease: A pilot study.

Gastroesophageal reflux disease (GERD) is a common medical condition, frequently refractory to medical therapy. Nickel is a leading cause of allergic contact dermatitis. Although nickel is widely found in foods, the effect of nickel on GERD is unknown. This pilot study sought to evaluate the effect of a low-nickel diet on GERD and determine if epicutaneous patch testing to nickel could predict responsiveness to a low-nickel diet. This prospective, single-site pilot study recruited 20 refractory GERD patients as determined by GERD Health-Related Quality of Life (GERD-HRQL) scores. All patients had epicutaneous patch testing for nickel and were then instructed to follow a low-nickel diet for 8weeks regardless of patch test results. GERD-HRQL was recorded at baseline and following 8weeks of a low-nickel diet. Demographic and clinical data associated with GERD and nickel allergy were recorded. A Wilcoxon signed-rank test and nonparametric analysis of longitudinal data were run to determine statistical significance in pre-and post- GERD-HRQL scores in nickel patch test-positive and negative groups. Nearly all (19/20 [95%]) participants reported reduced GERD symptoms after 8weeks on a low-nickel diet. Mean total GERD-HRQL, regurgitation, and heartburn scores declined (27.05 ± 16.04, 11.45 ± 6.46, 10.85 ± 8.29). Participants with positive vs. negative patch testing to nickel responded equivalently to a low-nickel diet. A low-nickel diet improves GERD symptoms, but responsiveness to a low-nickel diet does not correlate with epicutaneous patch testing to nickel. ClinicalTrials.gov number: NCT03720756.

Nickel: Intrinsic Skin Sensitization Potency and Relation to Prevalence of Contact Allergy.

Nickel remains the most commonly identified contact allergen. However, it has proven difficult to demonstrate significant skin-sensitizing activity for nickel in toxicology tests, which typically have indicated a weak skin sensitization potential. Information indicates that in vivo assays are not predictive of dermal sensitization hazard or potency for nickel due to a human-specific mechanistic route for nickel sensitization that animals lack. A similar rationale will apply to in vitro alternatives—although these currently have limited ability to determine intrinsic potency. Generally, in silico methods are not designed for metal allergens and cannot contribute to the analysis. For ethical reasons, human experimental work has been limited, with a single study suggesting moderate potency. Accordingly, it seems reasonable to conclude that the high frequency of contact allergy to nickel in humans is a function of both its intermediate potency coupled with a high level of dermal exposure, particularly to damaged/inflamed skin.

HLA-DR53 (DRB4∗01) associates with nickel sensitization

HLA-DR53 (DRB4∗01) associates with nickel sensitization

Eczéma de contact systémique au nickel d’une canule métallique de trachéotomie

Nickel-induced systemic contact dermatitis is rare. Herein we report a case of nickel-induced systemic contact dermatitis following use of a metal tracheostomy cannula. n 84-year-old female patient with a history of intolerance to costume jewelry presented diffuse pruritic erythematous rash 72hours after tracheostomy cannula insertion. Dimethylglyoxime testing of the metal tracheostomy cannula was positive and patch testing confirmed nickel sensitization. This is thus a case of nickel-induced systemic contact dermatitis caused by the release of nickel sulfate from a metal tracheostomy cannula that was resorbed via the tracheostomy lesion.

Symptoms of titanium and nickel allergic sensitization in orthodontic treatment

AimThe study aimed to evaluate to which extent self-reported symptomatology, age, and sex are predictors of titanium and nickel allergic sensitization in patients in treatment with fixed orthodontic appliances.MethodsThe study analyzed 228 subjects aged 11–45 years (median 18, interquartile range 16–22); 68% of them were females, and 52% were adolescents. The allergic sensitization testing included epicutaneous patch test to titanium, titanium dioxide, titanium oxalate, titanium nitride, and nickel sulfate. The questionnaire on symptoms potentially linked to titanium and nickel sensitization was used.ResultsPrevalence of the allergic sensitization to titanium in patients undergoing orthodontic treatment was 4% (2% only to titanium without nickel) while to nickel 14% (12% nickel without titanium). Hypersensitivity to both metals at the same time was present in 2% of subjects. Sensitization to nickel was more common in females than in males (17 vs. 8%) and much more common in adults than in adolescents with small effect size (20 vs. 8%; p = 0.013). Sensitization to titanium was more common in females than in males (6 vs. 1%) with no difference in age. Multiple logistic regression analysis revealed that adult age increases the odds for being sensitized to nickel for 2.4 × (95% CI 1.1–5.6; p = 0.044) while watery eyes for 3.7 × (95% CI 1.2–11.1; p = 0.022). None of the symptoms were significant predictors of titanium sensitization.ConclusionAllergic sensitization to titanium and nickel are not very frequent in orthodontic patients, and self-reported symptomatology is a weak predictor of those sensitizations.