Tag Archive | Metal hypersensitivity

Prosthetic Metal Allergies: The Mystery Continues

Metal Hypersensitivity for OBuzzThis basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Immunosensitivity to metallic implants has been recognized for years, with the principal research focus on joint arthroplasty components. While cutaneous metal allergies are relatively common (as prevalent as 20%), immunosensitivity to implanted metal is much less common.

On their own, metal ions in the body such as nickel and cobalt do not cause immune responses, although high levels can be toxic to specific organs. However, when these ions associate with proteins in the plasma they may form haptens. These molecules in turn may bring about delayed hypersensitivity reactions.

Reactions to metals appear to be type IV (delayed) hypersensitivity responses leading to activation of T-lymphocytes, which in turn release inflammatory cytokines. While Langerhans cells in skin respond to direct or indirect antigen presentation, we don’t know which cells are involved in intra- and extra-articular manifestations in total joint arthroplasty. The skin response may include eczematous and/or erythematous papular lesions; within the affected limb, pain, swelling, and stiffness may be regional responses.

Determining cause and effect remains problematic. We have not yet conclusively determined whether symptoms from joint implants are due to metal sensitivity.  The diagnosis of metal immunosensitivty is based on exclusion of complications such as infection, aseptic loosening, mechanical malalignment, and, less commonly, complex regional pain syndrome and overstuffing.

The two most utilized tests for implant metal allergies are cutaneous patch testing and lymphocyte transformation testing. Unfortunately, cutaneous testing may not reflect the process in the joint, and preoperative patch screening has not proven to be beneficial. Lymphocyte transformation testing is expensive, not validated, and unavailable for many.

Alternatives include use of implants coated with titanium nitride, zirconia nitride, or zirconium oxide, or the use of “hypoallergenic” metals such as titanium and oxinium. However, except in the setting of revision, the clinical and cost effectiveness of these metals remain to be confirmed. The one relative certainty related to this issue is to use alternative-metal implants in patients with known severe systemic or cutaneous metal sensitivity.


Nima Eftekhary, MD; Nicholas Shepard, MD; Daniel Wiznia, MD; Richard Iorio, MD; William J. Long, MD, FRCSC; and Jonathan Vigdorchik, MD. Metal Hypersensitivity in Total Joint Arthroplasty https://icjr.net/articles/metal-hypersensitivity-in-total-joint-arthroplasty

Arif Razak, BSc, MBChB, MRCS; Ananthan D. Ebinesan, MBChB, MRCS; Charalambos P. Charalambous, BSc, MBChB, MSc, MD, FRCS (Tr & Orth). Metal Hypersensitivity in Patients with Conventional Orthopaedic Implants. JBJS Reviews; 2014 Feb 4; 2 (2).10.2106/JBJS.RVW.M.00082

Editor’s Choice – March 3, 2014

Orthopaedic surgeons are frequently asked if the metal devices that they implant induce hypersensitivity reactions. In addition, during the workup of a patient who has an infection at the site of a loose prosthesis, the question of hypersensitivity reaction is frequently raised. Metal hypersensitivity, as detected with skin patch testing, is common. Several sources have suggested that the prevalence of metal hypersensitivity is between 10% and 17% in the general population. However, there is only anecdotal evidence that deep-seated metal implants may induce cutaneous sensitivity reactions.

In the February 2014 issue of JBJS Reviews, Razak et al. consider conventional arthroplasty implants (metal-on-polyethylene and metal-on-ceramic articulations) and fracture fixation devices. Their article does not address metal-on-metal arthroplasty, although they do consider articulating implants and the local and systemic levels of metal ions that they produce. The authors point out that, when considering metal hypersensitivity, it is important to distinguish between cutaneous contact sensitivity and sensitivity to deep-seated implanted devices.

Cutaneous hypersensitivity reactions to metal are mediated by activation of the immune system and can be divided into four types. Type-III reactions are antibody-mediated, and Type-IV reactions are cell-mediated. Identifying cutaneous metal hypersensitivity involves self-reporting, patch testing, dry metal tapping, subcutaneous metal implantation, lymphocyte transformation tests, and leukocyte migration inhibition tests.

Hypersensitivity to deep-seated implants is different. Conventional orthopaedic implants are usually made of alloys (mixtures of several metals), such as cobalt-chromium, stainless steel, titanium, and zirconium alloys. These alloys contain traces of other metals such as nickel, aluminum, and molybdenum. These deeply implanted metallic materials may corrode chemically or mechanically, resulting in the release of metal debris and ions that may combine with native proteins to form larger complexes. These larger complexes may then be taken up and presented by antigen-presenting cells.

As noted by Razak et al., there does not seem to be strong evidence supporting or disputing the role of metal hypersensitivity in the development of aseptic loosening, deep local reactions, or ongoing pain in patients with deep-seated implants. The levels of metal ions that are released vary between articulating and non-articulating implants, and there is a paucity of data to address the question of their role in the aseptic loosening process. Malfunctioning articulating implants can release high levels of metal ions, and fracture fixation devices are less likely to generate the same amount of metal ions as conventional arthroplasty implants. Therefore, the likelihood that fracture fixation devices are at play in the hypersensitivity process seems small.

On the basis of the data presented in this article, it remains unclear what role metal hypersensitivity plays in patient symptomatology, implant failure, or implant loosening. However, certain considerations should be taken into account when one is faced with a patient who is about to undergo orthopaedic surgery involving the use of a metal implant and who has a history or a question regarding sensitivity to metal. While several approaches can be used, most involve the use of patch testing at some point, despite the fact that this test is costly ($80.00 per kit in the United States).

Razak et al. recommend that, when the use of an orthopaedic metal implant is being considered, the patient should be counseled, as part of the consent process, with regard to the small risk of potential reactions to metal, the risk of ongoing symptoms and aseptic loosening, and the limitations in our understanding of the mechanisms that account for metal hypersensitivity reactions. In the rare case in which a patient reports a substantial localized reaction (such as blistering, hives, or extensive rash) or a systemic cutaneous reaction to metal, patch testing is recommended. Such patch testing should include components of potential implants such as stainless steel, cobalt-chromium, or titanium-zirconium.

To our knowledge, there have been no randomized controlled trials comparing stainless steel or cobalt-chromium implants with identical implants made of titanium or zirconium, so the need to provide high-quality evidence regarding the effects of implant materials on clinical outcomes is important. However, what is really needed is the development of tests that will reliably identify individuals who are prone to a response to a deep-seated metal implant, and these tests are simply not available.