Joris Muris

Transition metal sensing by Toll‐like receptor‐4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators

Background Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll‐like receptor (TLR)‐4.

Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity

Exposure to titanium (Ti) from implants and from personal care products as nanoparticles (NPs) is common. This article reviews exposure sources, ion release, skin penetration, allergenic effects, and diagnostic possibilities. We conclude that human exposure to Ti mainly derives from dental and medical implants, personal care products, and foods. Despite being considered to be highly biocompatible relative to other metals, Ti is released in the presence of biological fluids and tissue, especially under certain circumstances, which seem to be more likely with regard to dental implants. Although most of the studies reviewed have important limitations, Ti seems not to penetrate a competent skin barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some indications of Ti penetration through the oral mucosa. We conclude that patch testing with the available Ti preparations for detection of type IV hypersensitivity is currently inadequate for Ti. Although several other methods for contact allergy detection have been suggested, including lymphocyte stimulation tests, none has yet been generally accepted, and the diagnosis of Ti allergy is therefore still based primarily on clinical evaluation. Reports on clinical allergy and adverse events have rarely been published. Whether this is because of unawareness of possible adverse reactions to this specific metal, difficulties in detection methods, or the metal actually being relatively safe to use, is still unresolved.

Sensitization to palladium and nickel in Europe and the relationship with oral disease and dental alloys

The role of palladium and nickel sensitization in oral disease and dermatitis is not fully understood.

Sodium tetrachloropalladate for diagnosing palladium sensitization

Background. Exposure to palladium (Pd) may lead to clinical allergic reactions. With frequent nickel (Ni) exposure and cross‐reactivity between Ni and Pd at the T cell recognition level, positive Pd reactions on patch testing are surprisingly uncommon. PdCl2 is often used for epicutaneous patch testing.

Sensitization to palladium in Europe

Recently, sodium tetrachloropalladate (Na2PdCl4) was found to be a more sensitive palladium patch test allergen than palladium dichloride (PdCl2).

Palladium-induced Th2 cytokine responses reflect skin test reactivity

Recently, a crucial role of Th2 responses in nickel allergic contact dermatitis (ACD) was demonstrated. As palladium allergy is an issue of growing interest, the diagnostic potential of Th2 parameters for palladium sensitization was investigated. Palladium (Na2[PdCl4])‐induced lymphocyte proliferation (LPT), Th1 and Th2 cytokine production were correlated with skin test (ST) reactivity in 16 positive and 21 negative controls. Furthermore, the diagnostic potential of these assays was evaluated using receiver operating characteristics (ROC) analysis. For comparison, same experiments were carried out for nickel (NiSO4). Correlation coefficients between palladium ST reactivity and IFN‐γ, LPT, IL‐5, and IL‐13 were 0.34, 0.51, 0.69, and 0.78, and overall test accuracies were 68%, 81%, 89%, and 95%, respectively. Both palladium‐ and nickel‐mediated Th2 responses tightly correlate with ST reactivity, supporting recent findings on the crucial role of Th2 involvement in ACD. Therefore, these assays may have great potential as diagnostic tools for future in vitro sensitization testing.

Palladium-based dental alloys are associated with oral disease and palladium-induced immune responses

Palladium (Pd) and gold (Au) based dental alloys have been associated with oral disease.

Palladium allergy prevalence is underestimated because of an inadequate test allergen

A comprehensive review by Faurschou et al. on palladium allergy was recently published in Contact Dermatitis (1). However, we believe that important information on palladium allergy testing was overlooked. The authors only reviewed the patch test results for the commonly used test salt palladium dichloride (PdCl2). In our view, there are three arguments that question the sensitivity of PdCl2 as a test allergen. First, PdCl2 forms oligomeric or polymeric structures in water, making it poorly soluble; therefore, adequate skin penetration, which is necessary for patch testing, might be hampered. Second, as the article describes, there is in vivo and in vitro evidence supporting cross-reactivity between nickel and palladium. In cases of true cross-reactivity, the prevalence of palladium sensitization should equal the prevalence of nickel sensitization, which is not the case. Third, from a dentist’s point of view, some patients may be suspected of having palladium allergy. This suspicion is mainly based on local oral mucosal abnormalities in areas in contact with palladium containing dental restorative alloys, combined with a positive metal-allergic history. However, patch testing with PdCl2 often does not confirm this suspicion of palladium allergy. The low sensitivity of PdCl2 was considered in two articles on an alternative palladium test allergen, namely sodium tetrachloropalladate (Na2[PdCl4]), for patch testing (2) and for lymphocyte proliferation testing (3). Nine-fold and two-fold more reactivity to Na2[PdCl4] than to PdCl2 was found in suspected patients for in vivo and in vitro testing, respectively. The results of both studies confirm the theory of cross-reactivity between nickel and palladium. Furthermore, it has been suggested that Na2[PdCl4] be included in the recommended European baseline patch test series. The clinical relevance of positive patch test results is an issue of debate. The authors suggest that palladium allergy is of clinical relevance mainly in patients with oral disease. We underline this suggestion, but emphasize the low sensitivity of PdCl2 as a palladium test allergen, which is especially important in patients with oral diseases. Any review on palladium allergy should now mention Na2[PdCl4] as an alternative test allergen.

Influence of shape and finishing on the corrosion of palladium-based dental alloys

PURPOSE The purpose of this study was to evaluate the effects of the surface treatment and shape of the dental alloy on the composition of the prosthetic work and its metallic ion release in a corrosive medium after casting. MATERIALS AND METHODS Orion Argos (Pd-Ag) and Orion Vesta (Pd-Cu) were used to cast two crowns and two disks. One of each was polished while the other was not. Two as-received alloys were also studied making a total of 5 specimens per alloy type. The specimens were submersed for 7 days in a lactic acid/sodium chloride solution (ISO standard 10271) and evaluated for surface structure characterization using SEM/EDAX. The solutions were quantitatively analysed for the presence of metal ions using ICP-MS and the results were statistically analysed with one-way ANOVA and a Tukey post-hoc test. RESULTS Palladium is released from all specimens studied (range 0.06-7.08 µg·cm-2·week-1), with the Pd-Cu alloy releasing the highest amounts. For both types of alloys, ion release of both disk and crown pairs were statistically different from the as-received alloy except for the Pd-Ag polished crown (P>.05). For both alloy type, disk-shaped pairs and unpolished specimens released the highest amounts of Pd ions (range 0.34-7.08 µg·cm-2·week-1). Interestingly, in solutions submerged with cast alloys trace amounts of unexpected elements were measured. CONCLUSION Shape and surface treatment influence ion release from dental alloys; polishing is a determinant factor. The release rate of cast and polished Pd alloys is between 0.06-0.69 µg·cm-2·week-1, which is close to or exceeding the EU Nickel Directive 94/27/EC compensated for the molecular mass of Pd (0.4 µg·cm-2·week-1). The composition of the alloy does not represent the element release, therefore we recommend manufacturers to report element release after ISO standard corrosion tests beside the original composition.

Reactivity to sodium tetrachloropalladate (Na2[PdCl4]) compared to PdCl2 and NiCl2 in lymphocyte proliferation tests

Background:  For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross‐reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT).