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

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

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