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Evaluation and management of metal hypersensitivity in total joint arthroplasty: a systematic review. Acta Orthop Scand. In a study including 11 cases where periprosthetic tissue contained corrosive elements (solid chromium orthophosphate corrosion products) after aseptic loosening of articular implants, immune-response tissue reactions were identified in every case. Eur Ann Allergy Clin Immunol. Can metal implants cause autoimmune disease? [82], Implant properties may alter the amount of surface area available for metal ion release. (326):71-9. Murali Poduval, MBBS, MS, DNB is a member of the following medical societies: Association of Medical Consultants of Mumbai, Bombay Orthopedic Society, Indian Orthopedic Association, Indian Society of Hip and Knee SurgeonsDisclosure: Nothing to disclose. Pizzoferrato A, Ciapetti G, Stea S, Cenni E, Arciola CR, Granchi D, et al. Acta Derm Venereol. 2019 Jul 21. An immune response to a surgically implanted medical device begins immediately. Please pass on my bad experience so others don't suffer. [1, 2, 3]. [40] At present, the published data are insufficient to determine safe reference ranges for blood levels of cobalt and chromium, but in the unexposed population, normal ranges are below 10 nmol/L and below 5 nmol/L, respectively. [54, 55, 56]. Most hardware that is placed to fix a fracture or fuse a joint does not need to be removed and, in fact, will not cause any symptoms. [61] as compared with other modes of failure. Teo Wendy ZW, Schalock PC. [39] However, it is important to note that as many as 20% of periprosthetic joint infections are culture-negative. These changes in the collection are what ultimately lead to pain. 2019 Feb. 477 (2):353-360. [4] Screening itself may induce sensitization. Swiontkowski MF, Agel J, Schwappach J, McNair P, Welch M. Cutaneous metal sensitivity in patients with orthopaedic injuries. William J Hopkinson, MD, FACS, FAAOS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Society for Sports Medicine, Illinois Association of Orthopaedic Surgeons, Illinois State Medical SocietyDisclosure: Nothing to disclose. Desensitization (ie, a change from a positive result to a negative one) occurs in 0% of cases for chromium, 2.1% for nickel, and 3.8% for cobalt. Available at https://www.sciencedaily.com/releases/2014/10/141009153817.htm. X-rays may also identify the area of the hardware which is likely to be causing the symptoms. [QxMD MEDLINE Link]. Sensitization of patients receiving orthopaedic implants. It involves measuring the proliferative response of T lymphocytes after activation. [QxMD MEDLINE Link]. In this instance, symptoms can be treated with local padding, such as wearing a thick sock or using a local gel pad. Biomaterials. 1986 Apr. In most instances, these screws and plates do not create symptomsand remain permanently in the foot. [QxMD MEDLINE Link]. Clin Rev Allergy Immunol. [QxMD MEDLINE Link]. Do Men Still Wear Button Holes At Weddings? [15] Activated lymphocytes release cytokines (eg, interferon [IFN] gamma [QxMD MEDLINE Link]. [QxMD MEDLINE Link]. TimesMojo is a social question-and-answer website where you can get all the answers to your questions. Fujishiro T, Moojen DJ, Kobayashi N, Dhert WJ, Bauer TW. Second stainless steel implant in the patient's right hip. Bull Hosp Joint Dis. Contact with blood activates the coagulation systems, the complement system, platelets, and immune cells, resulting in a thrombus at the interface that is the transient provisional matrix. Metal sensitivity as a cause of bone necrosis and loosening of the prosthesis in total joint replacement. An infection can occasionally be the cause of pain as well, so your surgeon will evaluate patients for this potential problem. J Arthroplasty. Available at http://njhealth.multimedia-newsroom.com/index.php/2013/05/15/new-blood-test-finds-allergies-before-implant-surgery/. Again, 4 months postoperatively, the patient began to complain of similar right hip pain, though imaging showed good bone graft incorporation and fracture healing (see the image below). Atanaskova Mesinkovska N, Tellez A, Molina L, Honari G, Sood A, Barsoum W, et al. Research into the use of anti-immunogenic coatings on implants is promising. Amini M, Mayes WH, Tzeng A, Tzeng TH, Saleh KJ, Mihalko WM. Practitioners should have a low threshold for ordering advanced imaging, in that many of these patients are asymptomatic, and even low metal ion levels have been associated with local tissue reaction. 469 (4):1127-33. 4 (13):2026-36. for: Medscape. [QxMD MEDLINE Link]. If a hip replacement rejection is suspected, medical attention should be sought immediately so that the problem can be properly diagnosed and treated. [80] Cement wear particles are immunologically inert and have specifically been found not to cause a lymphocyte response in vitro Contact Dermatitis. The signs and symptoms of failure are as follows: Severe and unbearable pain in the operated knee joint. Contact Dermatitis. [52] On the other hand, inhibition of inflammatory cytokines is also a powerful method for reducing inflammation, inhibiting osteoclastogenesis, and preventing osteolysis and implant loosening. J Bone Joint Surg Am. [4] Nonmetallic materials can be organic or inorganic. I doubt you are rejecting the titanium. [39] though in patients with absolute contraindications for revision surgery, a 21-day course of topical corticosteroids may sometimes control symptoms. [4], In light of these contradicting studies, it is difficult for the orthopedic surgeon to make the diagnosis of symptomatic metal allergy with confidence. Traditionally, skin patch testing has been the standard screening test for metal hypersensitivity; it is cost-effective and technically simple. [3] These two groups of cells communicate via cytokines, signaling molecules, transcription factors, and receptors. Santavirta S, Konttinen YT, Bergroth V, Grnblad M. Lack of immune response to methyl methacrylate in lymphocyte cultures. Use a cotton bud to rub gently observe the colour on the bud. [QxMD MEDLINE Link]. The symptoms can be due to a screw or plate that rubs against a boot, or pain may be produced when the tendon or soft tissue structure rubs against the prominent screw or plate. At the first site (right hip), complete healing occurred, and the patient remained asymptomatic after the device was removed. 1990 Nov. 23 (5):325-30. [QxMD MEDLINE Link]. [QxMD MEDLINE Link]. J Bone Joint Surg Am. WebSearch for jobs related to Symptoms of body rejecting surgical hardware or hire on the world's largest freelancing marketplace with 22m+ jobs. [20, 30] Some 25% of patients with well-functioning prostheses have metal sensitivity. Sometimes, a dental surgeon may inadvertently place a dental implant too close to a nerve. Dermatitis. [52]. [QxMD MEDLINE Link]. Image shows the right hip after the hardware was removed. [6, 65] It is thought that antigen-presenting cells that are localized to the skin (dendrite cells) may handle antigens differently from those that are systemic (ie, macrophages and monocytes). How do you know if your body is rejecting surgical hardware? [63] Skin test results may not return to normal after metal removal. The presenting signs and symptoms of a nickel or other metal hypersensitivity to an implanted orthopedic device are variable but usually consist of the expected complaints of a patient with hardware failure. Case example. 2019 Aug. 21 (4):786-795. The authors used a lubricated surface micro/nanostructured implant in a rabbit model. (In other words, with a positive result, no migration occurs.) 2014 Aug 11. 1977 Nov. 97 (5):537-41. Persistence of these cytokines leads to excessive inflammation. [6] (See the image below.). What are the side effects of having titanium in your body? Acta Biomater. The causes of these skin immunologic reactions are unclear. Metal allergy was found with severe types of alopecia areata (AA) at the rate of 69.9% and the elimination of metal allergens from dental metals, cooking instruments lead to satisfactory hair regrowth and prevention of severe relapse of AA for the period of in average four years and four months at the rate of 75.5%. [QxMD MEDLINE Link]. Goodman SB. Usually, the M1 macrophages transform into M2 macrophages, which help regulate tissue remodeling. [QxMD MEDLINE Link]. Goldring SR, Clark CR, Wright TM. [QxMD MEDLINE Link]. Immune Response to Implants and Biomaterials, encoded search term (Immune Response to Implants and Biomaterials) and Immune Response to Implants and Biomaterials, Conduits for Vascular Reconstruction in the Pediatric Patient. 2021 Mar 11. In a prospective cohort study that included 597 patients with metal-on-metal hip resurfacing and total hip prostheses, Hart et al found that elevated blood levels of metal (ie, chromium and cobalt) ions were associated with an increased risk of implant failure. A negative immune response can lead to adverse pathology, including excessive inflammation, interference with healing, fibrous encapsulation, and implant Patients can present with localized dermatitis or rashes but also with systemic eczematous dermatitis. According to the National Institute of Health, allergic symptoms resulting from exposure to metals typically appear 24 to 48 hours after exposure. [4]. [49, 50, 2, 3] ; these macrophages release proinflammatory mediators such as interleukin (IL)-1, IL-6, IL-16, and tumor necrosis factor (TNF)- 1979. [1], The incidence of metal allergies is rising in the general population, probably as a consequence of increased exposure to metal from piercings, jewelry, and internal medical devices or dental restorations. 1990 Nov. 23 (5):378-9. The septic joint near the implanted hardware. [86] These coatings are not yet available for clinical use, 2018 Jan. 10 (1):e1. Image shows successful titanium total hip implant in the left hip. J Bone Joint Surg Am. Svejgaard E, Morling N, Svejgaard A, Veien NK. Final follow-up image after successful total hip replacement of the left hip. Early morning nausea. Middleton's Allergy: Principles and Practice. 2016 Jun 13. Carl N Graf, MD Orthopedic and Spine Surgeon, Illinois Spine Institute Steven I Rabin, MD, FAAOS Clinical Associate Professor, Department of Orthopedic Surgery and Rehabilitation, Loyola University, Chicago Stritch School of Medicine; Medical Director, Musculoskeletal Services, Dreyer Medical Clinic Elves MW, Wilson JN, Scales JT, Kemp HB. 2009 Jan. 5 (1):172-80. Int J Dermatol. [44], Implanted pulse generators (eg, pacemakers, gastric stimulators, and neurostimulators) are made with stainless steel, titanium alloy, platinum, and iridium but also with epoxy resins, polymethylmethacrylates (PMMAs), and isocyanates, all of which may be immunogenic in some patients. 75 (6):799-801. The causes of these different patterns of inflammation are unknown, but the association between the extent of inflammation and visible metal particles (but not zirconium particles) supports the concept of an immune reaction to metal, and it illustrates that the process is not specific to metal-on-metal constructs. [QxMD MEDLINE Link]. Deutman R, Mulder TJ, Brian R, Nater JP. WebCan surgical hardware rejection symptoms? [5], As many as 13% of people are sensitive to nickel, cobalt, or chromium 1996 May. 2021 Sep 1. 4 (5993):376-8. Systemic lupus erythematosus (Lupus). [4] Bone cement hypersensitivity can be challenging, and revision using cementless procedures does not guarantee relief of presenting symptoms. More research is clearly needed. Your skin has a natural barrier thats disrupted when it reacts to nickel and other allergens. It is likely that she did have a true metal sensitivity reaction causing clinical failure of hardware and disabling pain. [2]. A skin rash may develop over the metal device but is not always present. Adult reconstructive surgery. This includes infection due to the body rejecting the implant or hardware as well as failure of the hardware that is resulting in severe spinal instability. [QxMD MEDLINE Link]. Gordon PM, White MI, Scotland TR. WebCan surgical hardware rejection symptoms? Veien NK, Svejgaard E. Lymphocyte transformation in patients with cobalt dermatitis. Options for surgical treatment include the following: Revision joint replacement surgery in patients with metal-on-metal prostheses have worse outcomes with more complications when the revision is due to metal reactions Caicedo MS, Solver E, Coleman L, Hallab NJ. The hardware was not loose, and the fracture was stable and clinically healed. Use soothing lotions, such as calamine lotion, which may ease itching. 2020 Jan. 17 (1):41-56. [3] Larger pores decrease inflammation. Int Orthop. William J Hopkinson, MD, FACS, FAAOS Professor, Department of Orthopedic Surgery and Rehabilitation, Loyola University, Chicago Stritch School of Medicine; Chief of Joint Replacement Service, Department of Orthopedic Surgery, Loyola University Medical Center Contact Dermatitis. Merritt K, Rodrigo JJ. [39] If the skin patch test finding is positive, the patient can be designated as allergic. 1990 Mar. Galea VP, Laaksonen I, Connelly JW, Matuszak SJ, Nortje M, Madanat R, et al. Which Teeth Are Normally Considered Anodontia? WebRejection to the hardware is uncommon and generally would not just present with swelling alone. The patient's symptoms resolved shortly thereafter. Merritt K. Role of medical materials, both in implant and surface applications, in immune response and in resistance to infection. [4] Preoperative aspiration of synovical fluid for culture, cell count, and neutrophil percentage may also be included in the workup to rule out infection. Patients with joint replacements typically have symptoms of loosening, including pain and instability. [2]. The lymphocytes are then mixed with solutions of specific metal ions, such as nickel, chromium, cobalt, or titanium. [60]. When they do occur, titanium allergy symptoms can range from mild to severe and can include: Metallic taste in your mouth. When should surgical hardware be removed? [68, 69, 70, 71, 72, 73] The technical sophistication and high expense of the LTT for implant-related metal sensitivity has limited its use; therefore, few conclusions can be drawn. Hallab N, Jacobs JJ, Black J. Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays. Patients with metal-on-metal implants should be monitored for metal ion levels at intervals of 6-12 months. The skin allergic reaction to nickel looks like eczema. Preoperative skin patch testing is not typically recommended unless there is a strong suggestion of established sensitivity by history, because of the slight chance of sensitization and the high-cost/low-yield results expected. [5] Testing may also be indicated for patients in whom infection and mechanical factors have been ruled out as the cause of implant failure or for patients with localized rash, pain, swelling, or inflammation near or over the implant or systemic cardiac or neurologic symptoms. These coating substances can encourage attachment of host cells and a local immune response against the infectious organism Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, et al. Markel et al reported the use of a dual-mobility cobalt-chromium hip replacement prosthesis with which metal ion levels were undetectable or minimal after 1-2 years; in addition, percentages of B cells and T cells were normal, with no increase in CD16 inflammatory monocytes, indicating the absence of an immune response to the implant. During the revision surgery, debridement to remove the infection may be Metal sensitivities among TJA patients with post-operative pain: indications for multi-metal LTT testing. 2021 Dec. 24 (8):1307-1316. What does a correlation coefficient tell you? fever. However, patients with known symptomatic metal allergies do have poorer results. 29 (10):1494-500. [Full Text]. [4] Although skin patch testing does not predict the stability or failure of prostheses, failure rates of joint replacement have been shown to be four times higher in patients with symptomatic metal sensitivity than in those who did not have preoperative symptoms. [51], The clinical presentation of patients with metal implant reactions is often nonspecific. When implants degrade or corrode, the immune system also responds to surface changes and degradation products. [45, 15] but, paradoxically, can also provoke an immune response to the coating substances themselves. New York: McGraw Hill; 2021. The presentation may include dermatitis and skin reactions, joint pain, joint effusions, and decreased wound healing. 17 (6):2189-98. Swelling, pain, draining sinuses, and inflammation at the implant site may mimic infection. Unfortunately, control of the signaling pathways that regulate immune cytokines is difficult and complex, and further research is required before such control can be brought within reach. Titanium, molybdenum, and cobalt have low toxicity as compared with nickel and chromium, which can cause highly toxic intracellular changes. Int J Mol Sci. How do you know if your spouse is not happy? If this is not acceptable for symptom relief, then consideration should be given to removing the hardware after the fracture or fusion has fully healed. National Jewish Health. Many patients with implanted metal hardware have positive skin test results for those metals but nevertheless are completely asymptomatic. Allergy to Surgical Implants. Radiolucencies around the hardware, screw migration, and changedposition of the implant imply loosening that could be due to hypersensitivity to the metal or could be the catalyst that induces a robust immune response. Unusual skin cancer linked to chronic allergy from metal orthopedic implant. [2, 49]. 1994 Mar. [10, 17, 19, 20, 21, 22, 23, 24, 6, 25, 26, 27, 28, 29] However, there is a question as to whether metal sensitivity is the inciting event or whether a failing implant leads to a more robust immune response and possibly increased clinical testing for metal reaction. [QxMD MEDLINE Link]. Cystic changes, such as occur in osteolysis, may be seen (see the image below). Chronic allergic contact dermatitis promotes skin cancer. [49, 2, 51, 48] and clear damaged tissues from the area. Given the false-positive results of skin patch testing, blood samples were sent for MIF testing, which later confirmed nickel hypersensitivity (personal communication, Katharine Merritt, PhD, US Food and Drug Administration Office of Science and Technology). 49 (Pt 2):118-31. Contact Dermatitis. Some people report instability or feeling like their hip is going to give out. Nixon RL, Diepgen T. Contact dermatitis. Medscape Education. Nevertheless, it is clear that specific osteomodulatory characteristics of the implant contribute. 2008 Aug. 19 (8):823-35. Allergy in hip arthroplasty. Although some studies have found sensitization to metal implants to be prevalent, Diagnostic dilemmas of Titanium Hypersensitivity in patients with medical implants: a case series. Immune responses in patients with metal-on-metal hip articulations: a long-term follow-up. Hip pain, groin pain, or thigh pain are all signs that your hip replacement could have an issue, although other referred pains can cause these symptoms too. How do you know if your body is rejecting screws? Radiography demonstrated loosening and cutout of the hip lag screw, but the fracture was healing (see the image below). 1978 Aug. 99 (2):191-6. An immune response can develop against nonmetallic components of implants as well. Fujishiro et al identified an association between the extent of inflammation and the amount of visible metal particles and concluded that this relation implied the occurrence of an immune response to the metal. Donati ME, Savarino L, Granchi D, Ciapetti G, Cervellati M, Rotini R, et al. [QxMD MEDLINE Link]. WebSearch for jobs related to Symptoms of body rejecting surgical hardware or hire on the world's largest freelancing marketplace with 22m+ jobs. Initially, this may be treated with shoe modifications, padding over the area, and simple measures to reduce the local swelling and inflammation. Implants from different manufacturers have varying metal compositions (see the image below). The following tests are more difficult to obtain because many clinical laboratories do not run them. [5] It is common for metal hypersensitivity to present as a skin rash at the site of the implant, 105-16. Although prescreening all patients for metal hypersensitivity may be costly and its clinical relevance dubious, various specific laboratory tests, including the lymphokine migration inhibition factor (MIF) test, appear to be confirmatory. Arch Dermatol. [40] This serves as a screening test for the possible presence of asymptomatic local soft-tissue reaction. Polyelectrolye multilayer films from hyaluronic acid have been developed, with good early experimental results. Koutalos AA, Toms AP, Cahir JG, Smith EJ. Br J Dermatol. The effects of metal corrosion debris on immune system cells. 12:2995-3007. Metal sensitivity in patients treated for tibial fractures with plates of stainless steel. Osteoimmunology and Future Implant Design, https://www.sciencedaily.com/releases/2014/10/141009153817.htm, http://njhealth.multimedia-newsroom.com/index.php/2013/05/15/new-blood-test-finds-allergies-before-implant-surgery/, Illinois Association of Orthopaedic Surgeons, Limb Lengthening and Reconstruction Society, American Association of Hip and Knee Surgeons, American Academy of Allergy, Asthma and Immunology, American Orthopaedic Society for Sports Medicine, Association of Medical Consultants of Mumbai, Sigma Xi, The Scientific Research Honor Society. ScienceDaily. In the view of most authors, routine preoperative screening in patients with no symptoms of metal hypersensitivity is not usually indicated prior to implant placement. When a hydrophilic surface is combined with a rough surface topography, there is a synergistic effect that yields even greater release of anti-inflammatory cytokines. Other swelling. I had spinal fusion 7/30. My incision burst open, was on a wound vac for 8 weeks but wouldn't heal, had second surgery to clean and close the wound Clin Orthop Relat Res. [46]. Use of monosaccharides as a surface coating for implants could potentially hide the implant from the host immune response in a similar manner. https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMTIzMDY5Ni1vdmVydmlldw==, Macrophage colony-stimulating factor (M-CSF), Receptor activator of NF-B ligand (RANKL). What language do the Sardaukar speak in Dune? [2], Wettability is strongly associated with protein layer absorption, blood clot formation and fibrin formation. Can a trust deduct investment advisory fees in 2021? Local exposure of metallic surfaces also affects ion release and can be a factor in the development of hypersensitivity reactions secondary to an implant. Infection, nonunion, aseptic loosening, other inflammatory conditions, mechanical failure of the implant, and malalignment issues must be excluded first before the problem is assumed to be an allergic reaction. [63], Additionally, systemic contact dermatitis has been described when a patient becomes sensitized via the cutaneous route and cross-reacts systemically. Severely high serum cobalt or chromium levels can lead to systemic symptoms, cardiotoxicity, neurotoxicity, and may induce chromosomal abnormalities. [24], The issue of the clinical significance of sensitization to implanted metals has long been debated in the literature. Pain around the site of orthopedic implants has many causes, and before blame can be assigned to metal sensitivity or allergy, a thorough investigation must occur. WebThe most common symptoms associated with loosening or instability in the hip or knee joint include: pain, popping or clicking sound, sensation that your joint is moving in and out of its socket, partial hip dislocation (sublaxation), full hip dislocation, sensation of your knee giving out when you put weight on it, or Irrigation and debridement were performed, and the patient was treated with intravenous antibiotics until intraoperative cultures proved negative. Likely possibilities that may need to be considered include internal/ external 2016. Organic biomaterials include natural and synthetic polymers, polysaccharides, and proteinsfor example, chitosan, glycosaminoglycans, hyaluronic acid, collagen, and silk. Hardware that partially exits the skin (pins or Kirschner wires) Infections at the surgical site are one reason why a foot doctor would remove the hardware. Granchi D, Ciapetti G, Stea S, Cavedagna D, Bettini N, Bianco T, et al. For patient education resources, see Total Hip Replacement and Knee Joint Replacement. Electrospun fibers promote bone regeneration scaffolds by virtue of their similarity to natural collagen fibrils. Blood levels of cobalt and chromium are typically 30 and 45 nmol/L, respectively, in unilateral well-functioning hip prostheses but increase to 6550 and 3400 nmol/L in failed prostheses. Cell culture methods for testing biocompatibility. [58, 59] which leads to a cascade of cellular reactions (including activation of monocytes/macrophages, phagocytosis, and release of cytokines) that eventually lead to increased osteoclastic activity around the prosthesis. 1985 Nov. 13 (5):294-301. 2021 Jul. Hypersensitivity Reactions to Implanted Metal Devices: Facts and Fictions. 1974 Nov. 56-B (4):626-42. [QxMD MEDLINE Link]. [QxMD MEDLINE Link]. Activated platelets stimulate migration of monocytes, which differentiate into macrophages. [6, 17, 18, 19] others have taken an opposing viewpoint, concluding not only that hypersensitivity fails to develop St Louis: Mosby-Year Book; 1998. X-rays will reveal the hardware if it is metal (most screws are stainless steel or titanium). [QxMD MEDLINE Link]. 96 (13):1091-1099. Others may want them removed because of cancer risk or to avoid security metal detection. Plasma-spray coatings and grouting agents limit exposure and decrease ion release from the implant. Everness KM, Gawkrodger DJ, Botham PA, Hunter JA. Patients with joint replacement may present with loss of motion. It's a site that collects all the most frequently asked questions and answers, so you don't have to spend hours on searching anywhere else. Patients that have previously had surgery to fix a fracture or to fuse a bone of the foot and ankle may have retained hardware that can become prominent and/or creates discomfort. Local inflammatory symptoms similar to the symptoms of infection are also possible, including warmth, erythema, and swelling over the implant, though systemic complaints (eg, fever) are unlikely. Usually, rose gold and yellow gold doesnt contain nickel. WebHowever since surgery and more apparent 8 -10 weeks post surgery are the symptoms of rashing up in area of neck chest throat and site of plate, burning ears and throat, chronic pain in my neck and a feeling of burning and soreness in neck and spine. Anionic/neutral particles decrease inflammatory reactions, whereas cations increase inflammation. [QxMD MEDLINE Link]. 1975 Nov 15. [81] ; thus, the lymphokine MIF result couldbe negative in osteolysis. Schalock PC, Thyssen JP. [10, 18, 21] others have argued that even if a metal allergy exists, no adverse effects occur. [QxMD MEDLINE Link]. Hip Int. [Full Text]. [Full Text]. [39] After placement of metal implants, sensitization (ie, a change from a negative result to a positive one) occurs in 2.7% of cases for chromium, 3.8% for nickel, and 3.8% for cobalt. 2012 Mar. You are being redirected to
Allergy, Principles and Practice.