The shadow of nickel

In orthodontics it is common for us to find patients who are allergic or sensitive to nickel. Some of them are aware of it, others aren’t; Hence, asking if they have reactions or allergies to jewelry, earrings or bracelets… will be an easy and good start to detect them. However, this knowledge may not be so evident and we will need to dig a little further.
Nickel and titanium alloys are routinely used in orthodontics. The proportion of nickel in the alloys can vary from 8% in the case of stainless steel to 50% in nickel titanium.
As we will see, the patient’s understanding of the relevance of nickel allergy can go beyond orthodontic treatment itself.
In 2020 the European Commission requested an update from the European Food Safety Authority (EFSA) on the risks of consuming nickel in food and water, taking into account the new reference dose data. The conclusions are worth reading and end up recommending that it is necessary to deepen the knowledge of oral biocompatibility in humans with different doses of nickel, especially in individuals with a greater predisposition or sensitivity [14].
The prevalence of nickel allergy in Europe is estimated to be between 8-18% of the general population (more frequent in women) [15]. Sometimes it can be associated with allergies to other metals such as chromium, cobalt, palladium… [16]
After its absorption, nickel is widely distributed throughout the body, it can cross the blood-brain barrier, the placenta and be excreted in breastfeeding. It is eliminated through the urine and its half-life is around 30 hours. In the general population, below certain levels, it is considered innocuous; the problem arises in those individuals with high sensitivity (being able to go unnoticed for years) or in workers exposed to high doses [14].
The orofacial region is related to type I, III and IV allergies, but the most common form of allergy to dental biomaterials in the oral cavity are type IV contact reactions or hypersensitivity that do not usually manifest symptoms on first contact but rather upon continuous exposure to antigen. This hypersensitivity is an excessive reaction of the immune system to a normally harmless antigen.
At the oral level, the most common signs and symptoms are: gingival hyperplasia, angular cheilitis, thrush, desquamation of the oral and labial mucosa, mucositis, inflammation or tongue depapilation, burning, xerostomia, metallic taste, lichen planus, granulomatosis…
At a systemic level, hypersensitivity to metals has been related to: tinnitus, autoimmune disorders such as autoimmune thyroiditis, celiac disease, connective tissue diseases, non-ischemic cardiomyopathy, fibromyalgia, inflammatory bowel disease (Crohn’s and colitis) and irritable colon [16, 17]. In addition, it is known that Helicobacter pylori (related to stomach cancer) needs nickel ion to colonize in the stomach acid environment [25].
Bloating and abdominal pain, digestion problems, diarrhoea, skin changes (dermatitis) may be systemic signs associated with allergies due to ingestion of nickel-rich foods. Headaches, even though they are less common and are not specific signs of allergy, must be taken into account.
It has been observed that patients with celiac disease and a gluten-free diet can be related to an increase in nickel intake, typical of that diet, which ends up generating hypersensitivity, as well as a recurrence of extra-digestive symptoms [18].
Certain nickel-rich foods increase symptoms of gastroesophageal reflux disease (GERD); in fact, sensitivity to nickel is greater in patients with GERD [19].
This relationship is relevant because a bidirectionality between allergic sensitivity and GERD has been suggested, since reflux is an acid that induces immune changes in the mucosa and that generates comorbidity between GERD and atopic disorders such as rhinitis, asthma, sinusitis, atopic dermatitis or contact and eosinophilic esophagitis [23].
Nickel ions form complexes with endogenous proteins that activate the innate and adaptive immune systems, although the mechanisms that regulate immunotoxicity remain to be resolved. Thus, it can induce a deregulation of the NF-KB factor [14], which controls DNA transcription, which can be related to cancer, inflammatory, autoimmune diseases (rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, type I diabetes, chronic obstructive disease, and asthma), septic shock, viral infections, or inadequate immune development.
Currently, there is no evidence linking oral exposure to nickel with cancer in humans [14], however, some studies in this regard should be highlighted:
The role of nickel ion as an epigenetic inducer of cancer that generates DNA alterations through methylation or histonization, causing genetic silencing [20] has recently been added to the theory of cancer stem cells or hierarchical evolution related to chronic exposure to metals [21]. .
Nickel can alter the function of the HIF (multiple gene transcription factor) system by displacing Fe from dioxygenase enzymes, generating cellular hypoxia that can in turn induce cancer [24].
Tan et al. [22] specifically highlight the relationship of nickel with rectal cancer in a study that integrated toxic-genomic databases with genetic information (GWAS) through bioinformatic analysis of groups with colon and rectal cancer with control groups. They identified significant relationships between chemical agents and colorectal cancer.
Finally, and as researchers usually conclude, it will be necessary to continue investigating and publishing to find out a little more and not end up “nickel-plated”.