The Difficult, Frustrating Issue of Metal Allergy

    It is unclear how many patients with a failed knee replacement have developed a true allergic reaction to their implant – which confounds patients and surgeons alike.

    A segment of patients who undergo joint replacement surgery develop problems related to metal ion exposure.

    This is primarily seen in metal-on-metal (MoM) hip replacement patients, whose problems run the gamut from an allergic-type response to a local or systemic effect caused by the toxicity of the metal ions themselves.

    In MoM hip replacement, the magnitude of the metal debris and ion generation is several orders greater than what is seen in a metal-on-polyethylene knee replacement. So with regards to knee replacement, the discussion is largely focused on the allergic side of the spectrum rather than on the systemic toxicity and effects of the ions.

    MoM hip replacement patients most likely are probably demonstrating a Type IV delayed hypersensitivity. This can lead to pseudotumors, which are aggregates of necrotic tissue, metal debris, and activated macrophage and lymphocyte cells. A similar response has been documented in a few cases of knee replacement, but it does not seem to be as profound as what is seen in MoM hip replacement.

    This is a difficult and frustrating problem for the patient and the surgeon. Speaking at the ICJR East meeting in New York, Henry D. Clarke, MD, advocated a systematic approach to evaluating and managing the knee replacement patient with a suspected metal allergy.

    He said that before jumping to the diagnosis of a metal allergy in a failed knee replacement, the surgeon should consider and eliminate the more common differential diagnoses:

    • Instability – extension/flexion/global
    • Soft tissue impingement
    • Extensor mechanism complications
    • Component failure
    • Periprosthetic fracture
    • Aseptic loosening
    • Infection
    • Particulate disease
    • Malpositioning – rotational

    These conditions can be diagnosed with relatively simple interventions. A history, physical examination, and X-rays usually provide enough information to diagnose the first six problems. Infection requires further blood work and aspiration, and CT scans are helpful for evaluating patients with osteolysis or synovitis related to particulate and for evaluating component rotation.

    Even after this evaluation, the specific cause of the problem will not be identified for a few patients. Certain symptoms and objective findings may suggest metal allergy, although none are specific or diagnostic:


    • Pain
    • Swelling
    • Stiffness
    • Skin rash locally around the knee or systemically

    Physical examination

    • Effusion/synovitis
    • Decreased ROM
    • Skin rash
    • Exclude instability


    • Early loosening or osteolysis
    • Exclude alignment or sizing problems

    Historically, skin patch testing (SPT) has been used as a more specific test. However, skin testing activates a different mechanism than the Type IV hypersensitivity seen with metal allergy, and the concern is that skin testing may not accurately reflect the internal reaction to an implanted prosthesis. In addition, some metal substances tested have a local irritant effect that is not an allergic response; patients with an irritant reaction must be excluded.

    Between 10% and 20% of the population tests positive for contact to metal, such as nickel, cobalt, and chromium. After knee replacement, between 25% and 48% of patients with a well-functioning knee have a SPT that is positive for contact allergy, with the number increasing to 60% in patients with failed implants. However, it is unclear whether this increase is due to increased ions leading to sensitization, or if it reflects an allergy leading to the failure.

    Other tests for metal allergy in knee replacement, the lymphocyte transformation test (LTT) and the MELISA test, have been used, but neither has been found to have any diagnostic value. In fact, the results of the two tests can contradict each other – a positive response to an allergen on LTT can be negative on MELISA, and vice-versa.

    In his practice, Dr. Clarke screens patients preoperatively regarding possible metal allergy. If a patient has a history of metal allergy or rash from jewelry, he will consider using a ceramic or ion-bombarded titanium femur with an all-poly or titanium tibial component. However, Dr. Clarke does not find any value in routine screening with SPT or LTT.

    In patients requiring revision of a knee replacement, the components plus the stems and augments should be “hypoallergenic,” Dr. Clarke said. Additionally, it is important to remember that nickel allergy is not the only possibility: Allergies to bone cement, benzyl peroxide, and titanium have been reported.

    Dr. Clarke’s takeaway messages on possible metal allergy in knee replacement patients include the following:

    • Avoid routine screening with SPT or LTT in primary knee replacement, but consider asking patients about metal allergy.
    • In cases of a painful and swollen or stiff knee after knee replacement, perform a systematic evaluation that will exclude other intrinsic problems – such as instability, aseptic loosening, and infection – before considering metal allergy.
    • The issue of metal sensitivity/allergy in knee replacement needs more investigation.
    • SPT is probably not helpful after knee replacement.
    • LTT testing is not validated and should be used with caution.
    • Consider revision to ceramic or titanium components in cases of unexplained local dermatitis or unexplained recurrent effusion and pain.