Vanadium allergy following total knee arthroplasty.

Allergic reactions to metals following joint arthroplasty represent a rare and poorly understood phenomenon. Much is still unknown regarding the natural history of this complication, and how it can best be prevented and managed. We present a case of a 68-year-old woman who underwent a left total knee arthroplasty for treatment of osteoarthritis. After an initial uneventful postoperative course, she developed a troublesome erythematous rash both around the incision site and over her trunk. Blood testing revealed no evidence of infection and clinically her prosthesis was functioning well. Skin patch testing revealed positive results for vanadium (+) and palladium (+). Her cutaneous symptoms are currently being managed conservatively and have shown a partial response to topical steroids. Revision surgery remains a long-term treatment option should conservative therapy fail; however, it would require a custom-made prosthesis as no standard tibial component is free from vanadium.

Thymic cytoarchitecture changes in mice exposed to vanadium.

The thymus is a vital immune system organ wherein selection of T-lymphocytes occurs in a process regulated by dendritic and epithelial thymic cells. Previously, we have reported that in a mouse model of vanadium inhalation, a decrease in CD11c dendritic cells was observed. In the present study, we report on a thymic cortex-medulla distribution distortion in these hosts due to apparent effects of the inhaled vanadium on cytokeratin-5 (K5+) epithelial cells in the same mouse model - after 1, 2, and 4 weeks of exposure - by immunohistochemistry. These cells - together with dendritic cells - eliminate autoreactive T-cell clones and regulate the production of regulatory T-cells in situ. Because both cell types are involved in the negative selection of autoreactive clones, a potential for an increase in development of autoimmune conditions could be a possible consequence among individuals who might be exposed often to vanadium in air pollution, including dwellers of highly polluted cities with elevated levels of particulate matter onto which vanadium is often adsorbed.

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation.

Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.

Metal sensitivities among TJA patients with post-operative pain: indications for multi-metal LTT testing.

Metal sensitivity testing is generally the diagnosis method of last resort for aseptic painful implants with elevated inflammatory responses. However, the relationship between implant-related pain and implant-debris-related metal sensitization remains incompletely understood. Although a sensitivity to nickel alone has been used as a general measure of metal allergy, it may lack the specificity to correlate sensitivity to specific implant metals and thus to select a biologically appropriate implant material. In this retrospective study, we report the incidence of pain and nickel sensitivity in patients with total joint arthroplasties (TJAs) referred for metal sensitivity testing (n=2018). We also correlated the degree of nickel hypersensitivity to implant pain levels (none, mild, moderate, and high, using a scale of 0-10) and the incidence of sensitivity to alternative implant metals in highly nickel-reactive subjects. Most patients (>79%) reported pain levels that were moderate to high regardless of implant age, whereas patients with severely painful TJAs had a statistically greater incidence of nickel sensitivity over the short-term post-operative period (≤4 years). Patients with moderate pain scores (4-7) and high pain scores (≥8) also exhibited significantly higher sensitivity to nickel compared to patients with no pain and no implant (controls) (p<0.05). Highly nickel-sensitive subjects (SI>8) also showed incidences of sensitization to alternative materials such as cobalt, chromium, or molybdenum (57%) or aluminum or vanadium alloy (52%). These data suggest that painful TJAs caused by metal sensitivity more likely occur relatively early in the post-operative period (≤4 years). The incidences of sensitivity to alternative implant metals in only a subset of nickel-reactive patients highlights the importance of testing for sensitization to all potential revision implant materials.

Sensitivity to implant materials in patients undergoing total hip replacement.

Sensitivity to implant materials is an unpredictable event, which may contribute to the process leading to the failure of the total hip replacement (THR). The aim of the current study was to investigate the informative power of skin testing in detecting the sensitization to the implant components in patients undergoing THR. A consecutive series of 223 patients was enrolled in the study, including 66 candidates to THR, 53 with stable implant, and 104 with THR loosening. The patch testing was performed by using the most relevant components of cobalt-based alloys (CoCrMo), Ti-based alloys (TiAlV), and bone cements. The frequency of positive patch testing in preimplant patients did not differ from that observed after THR. Patients with CoCrMo-failed implant showed a significant low frequency of nickel-positive skin reaction, while patients with TiAlV-THR had a high incidence of vanadium-positive patch testing. The panel of haptens showed a good performance in the identification of patients known to have a contact dermatitis. With regard to the THR outcome, patch testing was not able to discriminate between stable and failed implant. Sensitivity to at least one hapten, namely bone cement, as well as the positive medical history of hypersensitivity, influenced negatively the THR survival. Our results show the reliability of patch testing for investigating the sensitivity to implant components. The cause-effect relationship between sensitization and negative outcome cannot be established, but the shorter lifespan of THR in patients who have a positive patch testing supports the significant role of this event in contributing to the implant failure.

Effects of cadmium and vanadium ions on antigen-induced signaling in CD4(+) T cells.

Heavy metal environmental pollutants modulate antigen-directed responses by T lymphocytes, but the molecular mechanisms by which certain metal ions exert their effects are only poorly understood. We tested the hypothesis that cadmium and vanadium ions alter antigen-induced T cell signal transduction pathways in CD4(+) T helper cells. We used CD4(+) primary T lymphocytes and splenic T cells from DO.11.10 T cell receptor transgenic mice. We determined the effects of cadmium chloride and sodium orthovanadate at concentrations that did not induce apoptotic cell death, but affected cytokine or proliferation responses to antigenic stimulation. We used electrophoretic mobility shift assays to measure effects of cadmium and vanadium ions on antigen-induced activation of the nuclear transcriptional regulator proteins, nuclear factor-kappaB, cyclic AMP response element binding protein, nuclear factor of activated T cells, and activator protein-1. Different signaling pathways lead to activation of these transcription factors. Our results suggest that the two heavy metal ions differentially affect signaling pathways. This knowledge will help in the development of molecular epidemiological assays.

Effects of heavy metal ions on resting and antigen-activated CD4(+) T cells.

Heavy metal environmental pollutants increase susceptibility of affected individuals to bacterial and viral infections, but the mechanisms responsible for this effect are not known. We established cellular in vitro systems to identify molecular targets for the action of heavy metal ions. We used two model systems to determine the effects of heavy metal ions on antigen-induced T lymphocyte responses. The first system was representative of primary antigen responses and utilized CD4(+) primary T lymphocytes derived from DO.11.10 T cell receptor transgenic mice. The second system represented a memory T cell phenotype and utilized the CD4(+) T helper 1 clone, pGL2. We measured the effects of the four heavy metals cadmium, lead, mercury, and vanadium on cytokine and proliferation responses by purified CD4(+) T cell to antigenic stimulation. Cytokine responses were differentially affected by lead and vanadium at concentrations that did not affect T cell proliferation in response to antigen. We also determined whether the metal ions induced apoptotic cell death. Mercury induced apoptosis at concentrations as low as 0.5 microM, whereas cadmium required a concentration of 100 microM. Lead (maximal concentration tested was 200 microM) and vanadium (100 microM) did not induce apoptosis. The results suggested that the different heavy metal ions differentially affected antigen-stimulated responses in T helper cells. These in vitro systems can now be applied to test whether heavy metal ions alter antigen-induced T cell signal transduction pathways in CD4(+) T helper cells.

Immunoregulatory properties of some heavy metals in physiology and pathology conditions. Part I.

The paper presents literature review dealing with the role of some trace metals in immunological processes of the body. The author took into consideration iron, zinc, magnesium, selenium, lithium and vanadium. They take part in the control of immunity processes nonspecifically potentializing the immunological response of modifying it in the presence of mitogens and antigens. The place where this interaction probably undergoes are the membrane receptors of lymphocytes and macrophages for mito- and antigens. The trace metals seem to control and reproduce their activity, taking part in the transport through the membranes of immunologically competent cells.