Nickels and tines: the myth of nickel allergy in intracranial stents

BackgroundMost intracranial stents contain nickel alloy, and nickel allergy or hypersensitivity is common. Neurological injury following endovascular treatment with a nickel containing intracranial stent has been reported in patients with purported nickel allergy, but it is unclear whether these reactions represent true nickel hypersensitivity. We quantified nickel release from commonly used intracranial stents to investigate whether such stents should be avoided in patients with nickel allergy.MethodsWe examined nickel release from seven commonly used intracranial stents: Enterprise, LVIS Jr, Neuroform, Wingspan, Zilver, Pipeline Flex Embolization Device, and Surpass Evolve. We incubated each stent in human plasma-like media for 30 days. Dimethylglyoxime (DMG) spot testing was performed on each stent to detect released nickel at 0 and 30 days. Inductively coupled plasma–optical emission spectroscopy (ICP-OES) was then used to quantify the nickel concentration of the media at 30 days. Nickel currency and nickel standard for atomic absorption spectrometry were used as positive controls.ResultsDMG spot tests indicated nickel release only from nickel currency at 0 and 30 days of incubation. No nickel release was detected from any stent at 30 days using ICP-OES.ConclusionsNickel release from commonly used intracranial stents is negligible. These results suggest that previously reported hypersensitivity to these stents may be misattributed to nickel allergy, and that patients with nickel allergy may be safely treated with select nickel-containing stents.

Real world experience with minimally invasive wireless percutaneous neuromodulation in a tertiary care centre

Background Wireless percutaneous nerve stimulation (PNS) for chronic pain is rapidly evolving in the ever expanding neuromodulation paradigm. Safety and lower risks with a potential of long-term analgesia cannot be over emphasised especially with the ongoing opioid pandemic. PNS with an implanted pulse generator (IPG) has also been shown to provide good benefit, without often unpleasant widespread paraesthesia from conventional spinal cord stimulators. Aim and Methods We retrospectively extracted data on all wireless PNS implants in our highly specialised pain neuromodulation centre since initiation of wireless PNS service in August 2019. Patient demographics, pain history, analgesic intake and details on implant follow-up data within 1 year post-implant including pain relief, EuroQol-5 Dimension (EQ-5D) and Patients’ Global Impression of Change (PGIC) scores were extracted. The cases are presented in a narrative format. Result A total of five patients were implanted with wireless (Stimwave®) PNS from August 2019 to February 2020. Neuropathic pain was the most common presenting diagnosis. All patients showed >50% pain relief at 3 months. EQ-5D and PGIC did not show any improvement in the subjects. Two of the patients managed to decrease their analgesics after implantation. Similar sustained benefits could not be demonstrated after 1 year. Discussion PNS can provide analgesia in appropriately selected cases. Naivety of the technique and procedure might cause some degree of uncertainty. External pulse generator with wireless transmission avoids IPG and tunnelling related side effects, but requires individualised special wearable technology to power the lead. Minimally invasive nature of the technique might be attractive and preferable for patients with complex medical issues, nickel allergy and poor general health who may otherwise be unsuitable for Spinal Cord Stimulation (SCS) with conventional hardware. Robust prospective controlled studies and RCTs in future might provide further insights on utility in other neuropathic pain diagnosis, long-term outcomes and acceptability compared to conventional SCS.

Nickel hypersensitivity and endovascular devices: a systematic review and meta-analysis

ObjectiveNickel allergy is common; endovascular specialists are often confronted with nickel allergic patients ahead of the implantation of endovascular devices, many of which are nickel-containing. Our aim was to elucidate whether nickel hypersensitivity is significantly associated with worse or adverse outcomes after placement of a nickel-containing endovascular device.MethodsInclusion criteria were: endovascular and transcatheter procedures for coronary, structural heart, neurovascular and peripheral vascular pathology involving nickel-allergic patients. All adverse outcomes were included as defined by included studies. A systematic review and meta-analysis were undertaken using a random-effects model. Searches of MEDLINE and EMBASE were conducted for articles published 1947–2019.Results190 records were identified, 78 articles were included for qualitative synthesis and 15 met criteria for meta-analysis. Patch-test confirmed nickel allergy was associated with an increased risk of adverse outcomes following implantation of a nickel-containing endovascular device (n=14 articles, 1740 patients; OR 2.61, 95% CI 1.41 to 4.85). This finding further was observed in coronary (n=12 articles, 1624 patients; OR 1.94, 95% CI 1.16 to 3.23) and structural heart subgroups (n=2 articles, 83 patients; OR 52.28, 95% CI 1.31 to 2079.14), but not in the neurovascular subgroup (n=1 article, 33 patients; OR 3.04, 95% CI 0.59 to 15.72) or with a patient-reported history of nickel allergy (n=2 articles, 207 patients; OR 2.14, 95% CI 0.23 to 19.70).ConclusionsPatch-tested nickel allergy is associated with an increased risk of adverse outcomes following endovascular device implantation and alternative treatment options should be considered. Specialists faced with patients’ self-reporting nickel allergy should consider proceeding to diagnostic patch-testing.

Diet Intervention Study through Telemedicine Assistance for Systemic Nickel Allergy Syndrome Patients during the COVID-19 Pandemic

Background: Restrictions due to the COVID-19 pandemic limited patients’ access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). Methods: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). Results: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. Conclusions: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

Semaphorin3A Promotes the Development of Nickel Allergy

Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. Semaphorin 3A (Sema3A), a member of the semaphorin family, is reported to be involved in various immune disorders. However, its role in metal allergy has not been clarified yet. Herein, we show that Sema3A promoted nickel (Ni) allergy by mediating tumor necrosis factor-alpha (TNF-α) production and mitogen-activated protein kinase (MAPK) activation in keratinocytes. Sema3A was upregulated in NiCl2-stimulated mouse keratinocytes and in Ni allergy-induced mouse ear tissue. TNF-α production and MAPK activation were altered when Sema3A was suppressed in keratinocytes. The specific deletion of Sema3A in keratinocytes alleviated Ni allergy and regulated the macrophage polarization towards an anti-inflammatory direction. Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy.

Sensing of Nickel(II) Ions by Immobilizing Ligands and Using Different SPEs

The aim of this paper is the development of a sensor for the quantification of nickel ions in food raw materials and foods. It is believed that about 15% of the human population suffers from nickel allergy. In addition to digestive manifestations, food intolerance to nickel may also have systemic manifestations, such as diffuse dermatitis, diffuse itching, fever, rhinitis, headache, altered general condition. Therefore, it is necessary to control this content of nickel ions for the health of the human population by developing a new method that offers the advantages of a fast, not expensive, in situ, and accurate analysis. For this purpose, bismuth oxide-screen-printed electrodes (SPEs) and graphene-modified SPEs were used with a very small amount of dimethylglyoxime and amino acid L-histidine that were deposited. A potentiostat that displays the response in the form of a cyclic voltammogram was used to study the electrochemical properties of nickel standard solution with different concentrations. The results were compared and the most sensitive sensor proved to be bismuth oxide-SPEs with dimethylglyoxime (Bi2O3/C-dmgH2) with a linear response over a wide range (0.1–10 ppm) of nickel concentrations. Furthermore, the sensor shows excellent selectivity in the presence of common interfering species. The Bi2O3/C-dmgH2 sensor showed good viability for nickel analysis in food samples (cocoa, spinach, cabbage, and red wine) and demonstrated significant advancement in sensor technology for practical applications.

Allergy Testing Has No Correlation with Intraoperative Histopathology from Revision Total Knee Arthroplasty for Implant-Related Metal Allergy

Lymphocyte transformation testing (LTT) is often used in the workup for possible metal allergy after total knee arthroplasty (TKA) but the correlation of this test with other diagnostic metal-allergy findings in patients undergoing revision TKA for suspected metal allergy has not been established. A single-center, single-surgeon cohort of 19 TKAs in which both components were revised for presumed implant-related metal allergy based on history, physical, and LTT testing, to nonnickel-containing implants were retrospectively identified. Histopathologic samples obtained intraoperatively were semiquantitatively analyzed using both the Hospital for Special Surgery (HSS) synovial pathology score and the Campbell aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL) score. As histopathology control group, we included in the study an additional cohort of 17 patients who received aseptic revision TKA and had no history of reported or tested metal sensitivity. All preoperative LTT results were highly reactive to nickel. However, this did not correlate with local periarticular tissue response in 18 of 19 cases which demonstrated a low HSS synovial score (mean: 3.8 ± 2.8, of a maximum score of 28) and the low Campbell ALVAL scores (mean: 2.5/10 ± 1.3, of a maximum score of 10). There were not any significant differences between the study group (suspected implant-related metal allergy) and the control group (nonsuspected implant-related metal allergy) in regard to (1) the Campbell score and (2) the HSS synovial inflammatory score. Knee Society Clinical Rating System (KSCRS) function score improved significantly after revision (mean postoperative increase: 34.0 ± 17. 2; p < 0.001), as well as mean visual analog scale (VAS) pain (mean postoperative decrease: 33.3 ± 26.4; p < 0.01) score. The short-term survival rate (at mean follow-up of 26.1 months) of this patient cohort was 100%. In this cohort of revised TKA patients with suspected nickel allergy based on clinical presentation and LTT positive results, intraoperative histopathology was essentially normal. However, all patients with suspected nickel allergy showed a significant clinical and functional improvement with excellent short-term survival rates. The clinical significance of a positive LTT needs further study.

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.