Contact Dermatitis

Hypersensitivity Reactions to Orthopedic Implants: What’s All the Hype?

Author and Disclosure Information

Hypersensitivity reactions to orthopedic implanted materials exist but are rare. Potential allergens include metals and bone cement components. Clinical presentation can include localized or generalized cutaneous reactions and noncutaneous reactions. Preimplant patch testing for implant hypersensitivity reactions (IHRs) is only recommended if metal allergy is strongly suspected; postimplant patch testing to relevant allergens can be completed if symptoms are concerning for implant hypersensitivity. The decision to remove or revise an orthopedic implant should be made as a joint decision between the surgeon and patient.

Practice Points

  • Common clinical presentations of orthopedic implant hypersensitivity reactions include localized cutaneous eruptions, generalized cutaneous eruptions, and noncutaneous reactions.
  • Allergens implicated in orthopedic implant hypersensitivity reactions include metals and bone cement components.
  • Routine preimplant patch testing for orthopedic hypersensitivity reactions is not recommended but can be performed when there is strong concern for metal allergy.
  • Postimplant patch testing should be performed when symptoms are consistent with potential orthopedic implant hypersensitivity reactions.



Hypersensitivity to metal implants remains a controversial field in contact dermatitis and patch testing. With positive reactions to nickel hovering around 20% in patch-tested populations,1 the question remains whether metal-allergic patients can safely receive metal implants. Unfortunately, large controlled studies are lacking, in part due to ethical concerns of knowingly placing a metal implant in a metal-allergic patient. Much of the focus of implant hypersensitivity reactions (IHRs) has been on orthopedic joints including hips, knees, and shoulders, as well as fixed orthopedic implanted materials such as screws and plates. However, there have been reports of IHRs to cardiac devices including defibrillators, pacemakers, and intracardiac devices; dental hardware including implants, crowns, dentures, and braces; and neurologic and gynecologic devices. For the purposes of this review, we will focus on IHRs to orthopedic implants.

Making the Case for IHRs

There are multiple case reports and series documenting likely orthopedic IHRs in the literature2-5; however, large prospective studies are lacking. Some of the largest series are from Danish registry studies. In 2009, Thyssen et al6 reviewed356 patients who had undergone both total hip arthroplasty and patch testing. Metal allergy frequencies were similar between patch-tested registry patients and patch test controls, showing no increase in positive patch tests to metals after receiving implants. Additionally, implant revision rates were comparable between registry patients with and without patch testing. The group concluded that the risk for revision after hip implantation in metal-allergic patients and the risk for development of metal allergy after implantation were both low.6 In 2015, Münch et al7 compared 327 patients who had undergone both total knee arthroplasty and patch testing and found that prevalence of allergy to nickel, cobalt, and chromium was similar between patients who had undergone revision surgery and those who had not; however, for patients who had 2 or more knee revisions, there was a higher prevalence of postimplant metal allergy. This study also showed that metal allergy identified before implantation did not increase the risk for postimplantation knee revision surgery or implant failure.7 These larger studies suggest that although individual cases of IHR exist, it is likely quite rare.

Patients have been found to have increased levels of chromium (serum and urine) and titanium (serum) following total hip arthroplasty.8 Additionally, metal wear particles have been identified in postmortem livers and spleens, which was more prevalent in patients with a history of failed hip arthroplasty.9 It is difficult to determine the meaning of this data, as the presence of metal ions does not necessarily indicate allergy or IHR. In 2001, Hallab et al10 pooled data from several implant cohort studies and concluded that in comparison to a baseline metal sensitivity prevalence of approximately 10%, patients with well-functioning implants had a metal sensitivity–weighted average of 25%, and those with poorly functioning implants had a weighted average of 60%. Again, positive patch testing to metals does not necessarily implicate allergy as the cause of implant failure.

Some small studies have shown that patients with evidence of metal hypersensitivity improve with revision. Zondervan et al11 reviewed results of 46 orthopedic revisions following painful total knee arthroplasty. Patients with knee pain and lymphocyte transformation testing (LTT) positive for metals received hypoallergenic revisions, and those with LTT negative for metals received standard revisions. The group who received hypoallergenic revisions had more pain reduction compared to the standard revision group (37.8% reduction in pain vs 27%). However, this study was limited in that the diagnosis of metal allergy was made entirely on results of LTT.11 In 2012, Atanaskova Mesinkovska et al12 described 41 patients who underwent orthopedic patch testing following implantation for symptoms including pain, dermatitis, pruritus, joint loosening, edema, and impaired wound healing. Fifteen (37%) patients had positive patch test reactions to metals, and 10 (67%) of them had reactions to metals that were present in their implants. Six (60%) of these patients had their implants removed and their symptoms resolved; the remaining 4 continued to experience implant symptoms.12 These studies support the existence of rare metal-related orthopedic IHRs and support the concept of proceeding with orthopedic implant revision when indicated, safe, and agreed upon by the surgeon and patient. However, as noted in the series by Zondervan et al,11 not every patient with confirmed metal allergy who undergoes revision improves, so an informed conversation between the patient and surgeon is mandatory.

Types of Orthopedic Implants

Orthopedic implanted materials consist of either dynamic (knees, hips) or static (screws, plates) components. Several generations of hip implants have evolved since the 1960s. First-generation implanted hips were metal-on-metal and had high rates of metal release and sensitization. Metal-on-plastic implants may be less likely to release metal but instead release large polyethylene wear particles. Second-generation metal-on-metal implants reportedly have lower wear rates. With these implants, wear particles are generated but are reportedly smaller than first-generation particles.13

Allergens in IHRs

Metals are the most commonly implicated allergens in orthopedic IHRs. Potentially relevant metal alloys include 316L stainless steel, cobalt-chromium-molybdenum steel, Vitallium alloy, titanium alloy, titanium-tantalum-niobium alloy, and Oxinium (Smith & Nephew).14,15 Each alloy contains several metals, which can include nickel, chromium, cobalt, manganese, molybdenum, iron, titanium, aluminum, vanadium, niobium, tantalum, and zirconium, among others. For example, 316L stainless steel contains iron, nickel, chromium, manganese, molybdenum, nitrogen, carbon, sulfur, silicon, and phosphorus, whereas Oxinium contains only oxidized zirconium and niobium.

Bone Cement
Bone cement also has been reported in cases of orthopedic IHRs and can contain several chemicals, including methyl methacrylate, N,N-dimethyl-p-toluidine, benzoyl peroxide, hydroquinone, and gentamicin.14 Other potential exposures include adhesives (cyanoacrylates) and topical antibiotics.


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