Cytokine Profile in Patients with Aseptic Loosening of Total Hip Replacements and Its Relation to Metal Release and Metal Allergy.

Metal release from total hip replacements (THRs) is associated with aseptic loosening (AL). It has been proposed that the underlying immunological response is caused by a delayed type IV hypersensitivity-like reaction to metals, i.e., metal allergy. The purpose of this study was to investigate the immunological response in patients with AL in relation to metal release and the prevalence of metal allergy. THR patients undergoing revision surgery due to AL or mechanical implant failures were included in the study along with a control group consisting of primary THR patients. Comprehensive cytokine analyses were performed on serum and periimplant tissue samples along with metal analysis using inductive coupled plasma mass spectrometry (ICP-MS). Patient patch testing was done with a series of metals related to orthopedic implant. A distinct cytokine profile was found in the periimplant tissue of patients with AL. Significantly increased levels of the proinflammatory cytokines IL-1ß, IL-2, IL-8, IFN-γ and TNF-α, but also the anti-inflammatory IL-10 were detected. A general increase of metal concentrations in the periimplant tissue was observed in both revision groups, while Cr was significantly increased in patient serum with AL. No difference in the prevalence of metal sensitivity was established by patch testing. Increased levels of IL-1ß, IL-8, and TNF-α point to an innate immune response. However, the presence of IL-2 and IFN-γ indicates additional involvement of T cell-mediated response in patients with AL, although this could not be detected by patch testing.

Electrochemical Screening Spot Test Method for Detection of Nickel and Cobalt Ion Release From Metal Surfaces.

BACKGROUND: Present screening methods to rapidly detect release of nickel and cobalt ions from metallic surfaces involve colorimetric dimethylglyoxime (DMG)- and disodium-1-nitroso-2-naphthol-3,6-disulfonate-based spot tests with a cotton bud. There is a risk of false-negative test reactions because test outcomes are dependent on the pressure, area, and duration of surface wiping. OBJECTIVE: The aim of the study was to develop a miniaturized electrochemical device that uses a voltage to accelerate nickel and cobalt release from the tested item and perform an initial validation. METHODS AND RESULTS: A device was built in plastic, and its performance was investigated using 0.5 mL of test solutions of, respectively, DMG and disodium-1-nitroso-2-naphthol-3,6-disulfonate. Cotton buds that had been wetted in test solution were pressed against different metal surfaces at various voltages (0-9 V) and a range of test durations (0-120 seconds). Duplicate testing for nickel and cobalt release was also performed on a sample of 163 jewelry items. CONCLUSIONS: This novel electrochemical device makes it possible to perform nickel and cobalt ion release testing without rubbing, thereby reducing interindividual differences in testing technique. The nickel testing with the device seemed to be superior to conventional DMG spot testing.

Experimental patch testing with chromium-coated materials.

BACKGROUND: Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. OBJECTIVES: To examine patch test reactivity to chromium-coated discs. METHODS: We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. RESULTS: Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. CONCLUSIONS: Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients.

Cobalt release and complications resulting from the use of dental prostheses.

BACKGROUND: Cobalt release from dental prostheses has been shown to elicit allergic reactions in cobalt-allergic patients. It is therefore important to investigate whether these prostheses are possible sources of sensitization. OBJECTIVES: To assess (i) cobalt release from dental prostheses and (ii) allergic reactions to components of dental prostheses, and (iii) to investigate the oral mucosa for inflammation 1-5 years after insertion of the prostheses. METHOD: Clinical oral examination was conducted in 66 patients with 84 dental prostheses. Cobalt release from 84 functional (used) and 32 non-functional (new) prostheses was investigated with the cobalt spot test. Contact allergy was assessed by patch testing. Smear tests for Candida spp. were performed in patients showing signs of inflammation of the oral mucosa. The prostheses were assessed for biological and technical complications. RESULTS: None of the functional prostheses released cobalt, whereas this was observed in 24 of 32 non-functional prostheses. None of the patients had contact allergy to cobalt. Of the 66 patients, 11 showed signs of inflammation of the oral mucosa, 2 had oral candidiasis, 16 had ill-fitting prostheses, and all had insufficient oral hygiene. CONCLUSIONS: Dental prostheses released cobalt during the fabrication stages, but not 1-5 years after insertion. No allergic reactions were observed. Signs of inflammation were related to candidiasis, insufficient oral hygiene, and ill-fitting prostheses.

Experimental skin deposition of chromium on the hands following handling of samples of leather and metal.

BACKGROUND: Chromium is an important skin sensitizer. Exposure to it has been regulated in cement, and recently in leather. Studies on the deposition of chromium ions on the skin as a result of handling different chromium-containing materials are sparse, but could improve the risk assessment of contact sensitization and allergic contact dermatitis caused by chromium. OBJECTIVES: To determine whether the handling of chromium-containing samples of leather and metal results in the deposition of chromium onto the skin. METHODS: Five healthy volunteers participated. For 30 min, they handled samples of leather and metal known to contain and release chromium. Skin deposition of chromium was assessed with the acid wipe sampling technique. RESULTS: Acid wipe sampling of the participants' fingers showed chromium deposition on the skin in all participants who had been exposed to leather (range 0.01-0.20 µg/cm(2) ) and in 3 of 5 participants after they had manually handled metal discs (range 0.02-0.04 µg/cm(2) ). CONCLUSIONS: We found that samples of leather and metal had the ability to deposit chromium on the skin at significant levels, in spite of a short duration of exposure.

Chromium allergy and dermatitis: prevalence and main findings.

The history of chromium as an allergen goes back more than a century, and includes an interventional success with national legislation that led to significant changes in the epidemiology of chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen's chemical properties, its potential exposure sources, and the allergen's interaction with the skin, and also provides an overview of the regulations, and analyses the epidemiological pattern between nations and across continents. We provide an update on the allergen from a dermatological point of view, and conclude that much still remains to be discovered about the allergen, and that continued surveillance of exposure sources and prevalence rates is necessary.

Chromium(VI) release from leather and metals can be detected with a diphenylcarbazide spot test.

BACKGROUND: Along with chromium, nickel and cobalt are the clinically most important metal allergens. However, unlike for nickel and cobalt, there is no validated colorimetric spot test that detects chromium. Such a test could help both clinicians and their patients with chromium dermatitis to identify culprit exposures. OBJECTIVES: To evaluate the use of diphenylcarbazide (DPC) as a spot test reagent for the identification of chromium(VI) release. METHODS: A colorimetric chromium(VI) spot test based on DPC was prepared and used on different items from small market surveys. RESULTS: The DPC spot test was able to identify chromium(VI) release at 0.5 ppm without interference from other pure metals, alloys, or leather. A market survey using the test showed no chromium(VI) release from work tools (0/100). However, chromium(VI) release from metal screws (7/60), one earring (1/50), leather shoes (4/100) and leather gloves (6/11) was observed. We found no false-positive test reactions. Confirmatory testing was performed with X-ray fluorescence (XRF) and spectrophotometrically on extraction fluids. CONCLUSIONS: The use of DPC as a colorimetric spot test reagent appears to be a good and valid test method for detecting the release of chromium(VI) ions from leather and metal articles. The spot test has the potential to become a valuable screening tool.

Nickel and cobalt release from children's toys purchased in Denmark and the United States.

BACKGROUND: Nickel is the most common allergen detected by patch testing in children. There is an increasing number of cases in children who have not had exposure to piercing. Although the clinical relevance of nickel patch test reactions in children is sometimes uncertain, continued vigilance to identify new sources of nickel exposure in this age group is important. Recent case reports have described allergic nickel contact dermatitis in children following exposure to toys, but the magnitude of this problem is unknown. OBJECTIVE: The aim of this study was to evaluate nickel and cobalt release from children's toys. METHODS: We purchased 212 toys in 18 different retail and online stores in the United States and Denmark. Nickel and cobalt release was tested using the dimethylglyoxime and cobalt screening spot tests. RESULTS: A total of 73 toys (34.4%) released nickel, and none released cobalt. CONCLUSIONS: Toys are a commonly overlooked source of nickel exposure and sensitization. Therefore, dermatologists, allergists, and pediatricians should consider the role of toys in their evaluation of children with dermatitis, and the parents of children with positive nickel patch test reactions should be told that toys may release nickel and be a potential chemical source in the manifestation of allergic contact dermatitis.

Failure of total hip implants: metals and metal release in 52 cases.

BACKGROUND: The pathogenesis of total joint replacement failure is multifactorial. One hypothesis suggests that corrosion and wear of alloys result in metal ion release, which may then cause sensitization and even implant failure, owing to the acquired immune reactivity. OBJECTIVES: To assess cobalt, nickel and chromium(VI) release from, and the metal composition of, failed metal-on-ethylene total hip replacements. MATERIALS/METHODS: Implant components from 52 revision cases were evaluated with spot tests for free nickel, cobalt, and chromium (VI) ions. Implant composition was determined with X-ray fluorescence spectroscopy, and information on the reason for revision and complications in relation to surgery was collected from the medical charts when possible (72%). For 10 implants, corrosion was further characterized with scanning electron microscopy. RESULTS: We detected cobalt release from three of 38 removed femoral heads and from one of 24 femoral stems. Nickel release was detected from one of 24 femoral stems. No chromium(VI) release was detected. CONCLUSIONS: We found that cobalt and nickel were released from some failed total hip arthroplasties, and corrosion was frequently observed. Metal ions and particles corroded from metal-on-polyethylene may play a role in the complex aetiopathology of implant failure.

Consumer leather exposure: an unrecognized cause of cobalt sensitization.

BACKGROUND: A patient who had suffered from persistent generalized dermatitis for 7 years was diagnosed with cobalt sensitization, and his leather couch was suspected as the culprit, owing to the clinical presentation mimicking allergic chromium dermatitis resulting from leather furniture exposure. MATERIALS AND METHODS: The cobalt spot test, X-ray fluorescence, inductively coupled plasma mass spectrometry and scanning electron microscopy were used to determine cobalt content and release from the leather couch that caused the dermatitis and from 14 randomly collected samples of furniture leather. RESULTS: The sample from the patient's leather couch, but none of the 14 random leather samples, released cobalt in high concentrations. Dermatitis cleared when the patient stopped using his couch. CONCLUSIONS: Cobalt is used in the so-called pre-metallized dyeing of leather products. Repeated studies have found high levels of cobalt sensitization, but not nickel sensitization, in patients with foot dermatitis. We raise the possibility that cobalt may be widely released from leather items, and advise dermatologists to consider this in patients with positive cobalt patch test reactions.