Orthopedics

Feature Article 

Self-Reported Metal Allergy and Early Outcomes After Total Knee Arthroplasty

Kenneth J. Schmidt, MD; Philip S. Huang, DO; Clifford W. Colwell Jr., MD; Julie C. McCauley, MPHc; Pamela A. Pulido, BSN; William D. Bugbee, MD

Abstract

The impact of self-reported metal allergy (SRMA) in total knee arthroplasty (TKA) remains controversial. In the absence of objective tests, SRMA is often used as a screening tool for implant selection. The objective of this study was to determine the effect of SRMA on early outcomes after TKA. Between 2010 and 2014, 168 patients with SRMA underwent TKA; 150 (89%) received nickel-free implants, and 18 (11%) received cobalt-chrome implants that contained nickel. Mean age was 67 years, and 95% were female. A cohort of 858 TKA patients (mean age, 68 years) without SRMA matched by sex served as the control group. Outcomes included Knee Society Score (function [KSS-F] and knee [KSS-K]), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, knee flexion, further surgery, and complications. No differences were seen in KSS-F and KSS-K between patients with and without SRMA. The mean WOMAC pain scores were 89.1 for patients with SRMA and 85.2 for patients without SRMA (P=.030). Stiffness and physical function scores were similar. Knee flexion was similar. No differences were found between nickel-free and cobalt-chrome SRMA groups. Patients with SRMA and those without demonstrated similar early functional outcomes. Patients with SRMA who received standard cobalt-chrome implants had no significant difference in functional outcomes compared with patients with nickel-free implants. Better identifiers of patients at risk for adverse events due to implant material are needed. [Orthopedics. 2019; 42(6):330–334.]

Abstract

The impact of self-reported metal allergy (SRMA) in total knee arthroplasty (TKA) remains controversial. In the absence of objective tests, SRMA is often used as a screening tool for implant selection. The objective of this study was to determine the effect of SRMA on early outcomes after TKA. Between 2010 and 2014, 168 patients with SRMA underwent TKA; 150 (89%) received nickel-free implants, and 18 (11%) received cobalt-chrome implants that contained nickel. Mean age was 67 years, and 95% were female. A cohort of 858 TKA patients (mean age, 68 years) without SRMA matched by sex served as the control group. Outcomes included Knee Society Score (function [KSS-F] and knee [KSS-K]), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, knee flexion, further surgery, and complications. No differences were seen in KSS-F and KSS-K between patients with and without SRMA. The mean WOMAC pain scores were 89.1 for patients with SRMA and 85.2 for patients without SRMA (P=.030). Stiffness and physical function scores were similar. Knee flexion was similar. No differences were found between nickel-free and cobalt-chrome SRMA groups. Patients with SRMA and those without demonstrated similar early functional outcomes. Patients with SRMA who received standard cobalt-chrome implants had no significant difference in functional outcomes compared with patients with nickel-free implants. Better identifiers of patients at risk for adverse events due to implant material are needed. [Orthopedics. 2019; 42(6):330–334.]

Total knee arthroplasty (TKA) is a successful procedure for end-stage osteoarthritis of the knee. Most patients are satisfied with their outcome, and there have been reports of up to 97% survivorship at 10 years.1 However, up to 20% of patients are not satisfied and may ultimately require revision procedures.2 Common reasons for revision include infection, instability, component malposition, aseptic loosening, stiffness, and unexplained pain.3 Some debate exists regarding revision TKA for suspected or documented metal sensitivity. The exact mechanism by which metal sensitivity leads to a poor outcome is somewhat unclear, but metal allergy has been well documented by a large number of case reports.4–7 Metal allergy is mediated through a delayed type IV hypersensitivity reaction.8 Manifestations of metal sensitivity in humans include cutaneous reactions for skin contact and local reactions such as synovitis and continued pain according to case reports of TKA failure. The exact role that metal sensitivity plays in the outcome of TKA remains controversial. Nickel is the most common metal ion contributing to metal sensitivity, followed by cobalt and chromium.8,9

Several tests may aid in confirming a metal allergy, including skin patch testing and lymphocyte transformation testing. These invasive and costly methods are not commonly employed in the evaluation of patients undergoing TKA.8 Alternatively, patients' “self-reporting” of metal allergy may be used by surgeons to guide implant choices, causing them to consider the amount of nickel content. Most standard total knee components contain a combination of the following metal alloys in a variety of compositions: cobalt (Co), chromium (Cr), molybdenum, nickel (Ni), titanium, beryllium, vanadium, and tantalum.10 The Co, Cr, and Ni content of total knee components varies depending on manufacturer, and the Ni content may be significantly less or nonexistent in some designs (Table 1). Cobalt-chrome total knee implants conform to American Society for Testing and Materials standards and contain approximately 0.5% Ni, 27% to 30% Co, and 58% to 68% Cr.11 Titanium implants usually contain approximately 0.1% Ni, less than 0.02% Cr, and less than 0.01% Co.11 Alternative implants such as oxidized zirconium contain less than 0.0035% Ni, less than 0.02% Cr, and less than 0.002% Co.11 A previous study reported that the incidence of self-reported metal allergy (SRMA) in patients in a single-surgeon cohort was 14% (22% for women and 2% for men).12 Self-reported metal allergy has been found to be inaccurate when confirmed with patch testing.13

Metal Composition of Total Knee Arthroplasty Componentsa

Table 1:

Metal Composition of Total Knee Arthroplasty Components

To the current authors' knowledge, clinical outcomes following TKA among patients with SRMA who have various combinations of Co, Cr, or Ni implants have not been studied. The purpose of this study was to (1) calculate the incidence of SRMA in the authors' TKA patient population, (2) assess whether patients with SRMA had worse early outcomes following TKA compared with patients who did not have SRMA, and (3) ascertain whether patients with SRMA who received a standard CoCr TKA implant had worse outcomes than those who received a Ni-free implant. The authors hypothesized that patients with SRMA undergoing TKA with an implant containing Co, Cr, or Ni would have outcomes similar to those who had a CoCr/Ni-free component.

Materials and Methods

The authors' institutional review board–approved arthroplasty database contains comprehensive data on 10,853 primary TKAs. All patients consented to participate in the database. In 2010, the authors began routinely asking patients preoperatively, at an initial history and physical examination, if they had an allergy to metals. Responses were captured dichotomously (yes/no). Although patients had the opportunity to expand and clarify their response (eg, type of metal, severity, and number of reactions to metal), no standard follow-up question or further testing was employed for patients responding “yes.” Of the 2922 patients undergoing primary TKA from 2010 to 2014, 223 (7.6%) reported a metal allergy. Of the 223 SRMA patients, 168 had a minimum follow-up of 1 year and were included in the current study. Mean age was 67 years, and 95% were female. Of the 168 patients with SRMA, 150 (89%) received a Ni-free implant (Oxinium; Smith & Nephew, Memphis, Tennessee) and 18 (11%) received an implant containing CoCr. A cohort of 858 patients without SRMA who underwent primary TKA from 2010 to 2014 and had a minimum follow-up of 1 year matched by sex were included as the control group (no SRMA).

Postoperative Outcome Measures

Outcome measures included Knee Society Score for function (KSS-F) and knee (KSS-K) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The KSS-F and KSS-K range from 0 to 100, with higher scores representing the best possible outcome. The WOMAC physical function, stiffness, and pain scores also range from 0 to 100, but lower scores represent better outcome. Knee flexion was captured postoperatively. Further surgery and postoperative complications involving the operative knee were documented. Outcome measures collected at latest follow-up were included for analysis.

Statistical Analysis

Means and frequencies were used to summarize patient demographics and the occurrence of SRMA. Independent samples t tests were used to compare KSS and WOMAC scores and knee flexion between the SRMA and no SRMA groups, as well as between the Ni-free and CoCr SRMA cohorts. SPSS version 13.0 software (IBM, Armonk, New York) was used for all analyses. P=.05 was used to determine statistical significance.

Results

Mean follow-up was 2.1 years for patients with SRMA who received CoCr implants, 2.6 years for patients with SRMA who received Ni-free implants, and 1.6 years for patients with no SRMA. The KSS-F and KSS-S did not differ between the SRMA and no SRMA groups (Table 2). The WOMAC physical function and stiffness scores did not differ between groups, but the mean pain score was higher (representing more pain) in the SRMA group compared with the no SRMA group (89.1 and 85.2, respectively; P=.030). Knee flexion was similar in the SRMA and no SRMA groups (119.3° and 120.2°, respectively; P=.434). No patient had further surgery following TKA, and no early postoperative complications were reported within 1 year.

Postoperative Outcome Scores Among Patients With and Without Self-Reported Metal Allergy

Table 2:

Postoperative Outcome Scores Among Patients With and Without Self-Reported Metal Allergy

Within the SRMA group, pain, stiffness, and function were similar between those with a Ni-free implant and those with a standard CoCr implant (Table 3). Knee flexion was also similar, with patients receiving a Ni-free implant having a mean flexion of 119.6° and patients receiving a CoCr implant having a mean flexion of 117.7° (P=.416).

Postoperative Outcome Scores Among Patients With Self-Reported Metal Allergy Who Received a Nickel-Free Implant Versus a Cobalt-Chromium Implant

Table 3:

Postoperative Outcome Scores Among Patients With Self-Reported Metal Allergy Who Received a Nickel-Free Implant Versus a Cobalt-Chromium Implant

Discussion

In this patient database from 2010 to 2014, the prevalence of SRMA was 7.6%, which is consistent with previously published data.8,12 The current data suggest no difference in early functional outcomes between patients with and without SRMA. These results are in contrast to those of Nam et al,14 who reported a worse functional outcome for patients with SRMA. The current authors found that, among patients with SRMA, those who had a Ni-free implant had functional outcomes similar to those who had a CoCr implant.

Controversy exists regarding both the diagnosis and the importance of metal allergy and orthopedic implants. No gold standard currently exists for the detection of metal sensitivity. Options include skin patch testing and lymphocyte proliferation, but these tests are expensive and time consuming. In skin patch testing, dermal Langerhans cells are the antigen presenting cells that cause an inflammatory reaction. There are no Langerhans cells within the knee joint; as a result, this test does not mimic the interaction that metal implant ions have with local deep tissues. Multiple studies have investigated a correlation between skin patch testing and outcomes or failures following TKA. Bravo et al15 reported that skin patch testing was not predictive of worse outcomes after TKA at an average follow-up of 5.3 years. Granchi et al16 showed that a positive patch test for metal ion did not correlate with implant loosening in TKA. An alternative method of evaluation for metal sensitivity is the lymphocyte proliferation test. This in vitro test challenges lymphocytes to metal ions and quantifies a response. Regarding this methodology, it has not been extensively reported on in the orthopedic literature, it is not routinely used, and no conclusions can be reached regarding its utility in the TKA population.8

To the authors' knowledge, this is one of the largest investigations to evaluate clinical outcomes in patients with SRMA. The purpose of this study was to determine whether patients with SRMA had worse outcomes independent of a true metal allergy. All patients in this study were screened for a subjective metal sensitivity at their preoperative visit. One prior study followed 18 patients with SRMA to Ni who received Ni-containing implants for an average of 6.3 years and reported no failures.17 The authors did not assess functional outcomes for these patients. The current findings also differ from those of two previous studies regarding functional outcomes and SRMA. Nam et al14 found that patients with SRMA had worse KSS and SF-12 PC scores. Hinarejos et al18 found similar results, with worse KSS and WOMAC scores in the SRMA group.

Most patients at the authors' institution who report a metal allergy receive a Ni-free implant. For unknown reasons, 18 patients with SRMA received standard CoCr TKA implants containing some amount of Ni. Neither group showed a significant functional difference when compared at 2 years postoperatively. Multiple prior reports indicate improved outcomes after TKA revision to a ceramic component following suspected metal allergy.4–7 Although the current authors do not refute that this clinical entity exists, the best detection and treatment methods for metal allergy remain uncertain. The potential exists to incrementally improve outcomes if information regarding allergy or sensitivity to metal ions can be clarified for patients requiring TKA.

Limitations of this study included its retrospective nature and limited power and the short-term functional assessment of outcomes. A retrospective evaluation remains the only feasible way to study this patient population, as it would be difficult to randomize patients with a SRMA to a group that would receive a CoCr/Ni-containing implant. Although the authors have reported on the largest cohort of patients with SRMA to receive a Ni-containing implant, this study was underpowered to detect what may be a small but significant clinical difference in outcomes. There was a slightly higher percentage of female patients (95%) than in prior reports,19 which was likely due to a higher female prevalence and more frequent exposure to jewelry or Ni-containing products leading to an increase in self-reported metal sensitivity.12 A true allergic response or hypersensitivity to an implant would likely manifest itself or demonstrate any meaningful clinical difference within 2 years.

Conclusion

Metal hypersensitivity remains a topic of debate and a relatively rare clinical entity. In contrast to prior studies, the current data suggest that patients with SRMA had no difference in early clinical outcomes compared with patients without SRMA.16,18 Patients with SRMA who received a CoCr/Ni-free implant had clinical outcomes similar to those of SRMA patients with Ni-containing implants and patients without SRMA. Considering current evidence and the demonstrated equivalent clinical outcomes, the use of a CoCr/Ni-free TKA implant for patients with SRMA is reasonable but not required.

References

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Metal Composition of Total Knee Arthroplasty Componentsa

Total Knee Arthroplasty ComponentMetal Composition

CobaltChromiumNickel
Triathlon (Stryker, Mahwah, New Jersey)50% to 70% (balance)27.5% to 28.5%0.5%
Persona (Zimmer, Warsaw, Indiana)50% to 70% (balance)26% to 30%1.0% max
Sigma (DePuy, Warsaw, Indiana)50% to 70%27% to 30%0.5%
Oxinium (Smith & Nephew, Memphis, Tennessee)<0.002%<0.02%<0.0035%

Postoperative Outcome Scores Among Patients With and Without Self-Reported Metal Allergy

MeasureMean±SDP

SRMA (N=168)No SRMA (N=858)
Knee Society Score functiona74.1±23.474.0±21.4.989
Knee Society Score kneea84.4±13.386.9±13.6.069
WOMAC physical function scoreb86.3±16.584.1±19.7.276
WOMAC stiffness scoreb76.9±23.173.8±21.5.192
WOMAC pain scoreb89.1±15.985.2±17.2.030

Postoperative Outcome Scores Among Patients With Self-Reported Metal Allergy Who Received a Nickel-Free Implant Versus a Cobalt-Chromium Implant

MeasureMean±SDP

Nickel-Free Implant (N=150)Cobalt-Chromium Implant (N=18)
Knee Society Score functiona73.0±23.782.8±18.6.094
Knee Society Score kneea84.1±13.386.5±13.2.497
WOMAC physical function scoreb85.9±16.889.7±13.9.097
WOMAC stiffness scoreb75.8±22.786.6±25.1.411
WOMAC pain scoreb89.1±15.989.6±16.2.899
Authors

The authors are from the Division of Orthopaedic Surgery (KJS, PSH, WDB) and the Shiley Center for Orthopaedic Research and Education (CWC, JCM, PAP), Scripps Clinic, La Jolla, California.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: William D. Bugbee, MD, Division of Orthopaedic Surgery, Scripps Clinic, 10666 N Torrey Pines Rd, MS116, La Jolla, CA 92037 ( Bugbee.William@scrippshealth.org).

Received: November 18, 2018
Accepted: November 26, 2018
Posted Online: September 12, 2019

10.3928/01477447-20190906-01

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