Metal Allergy in Total Knee Arthroplasty

44 Metal Allergy in Total Knee Arthroplasty

Amit Atrey MD MSc FRCSC

Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

Clinical scenario

  • A 65‐year‐old female, otherwise healthy, with end‐stage osteoarthritis of her knee, undergoes an uncomplicated total knee arthroplasty (TKA) with a cobalt‐chrome (Co‐Cr) cemented prosthesis. The patella is resurfaced as well. The patient is discharged home after two days and within a few days postoperatively her range of motion (ROM) is 0–130°. At the six‐week follow‐up, ROM is the same with no effusions; the scar has healed properly and the patient is satisfied with the results. However, at the six‐month follow‐up, she presents with a painful knee, reduced ROM, mild effusion, and localized erythema.
  • X‐rays show no obvious loosening. Computed tomography (CT) reveals correct alignment of the components and infectious workup is negative including erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), white blood cell (WBC) count, and cultures. Arthroscopic arthrolysis is performed, revealing adhesions and synovitis. At the end of the operation the ROM is restored. All samples are negative for infection. Passive and active physiotherapy is initiated and pain is controlled.
  • The patient’s overall condition improves, but at the 12‐month follow‐up (six months post arthroscopy) she returns with a similar picture: effusion, localized erythema, reduced ROM, and pain. Once more infection is ruled out, and no evidence of implant loosening is detected.


The number of TKAs is increasing annually worldwide as a consequence of aging and higher rates of secondary osteoarthritis in the younger population.1 Despite the technological advancement, as well as the expertise of the surgeons, some reports state that almost 20% of patients with well‐fixed, properly aligned knee implants are not satisfied for various reasons.2 Additionally, some experience pain and stiffness for which no readily available explanation exists.3

Type IV hypersensitivity reaction, on the other hand, is mediated by T‐cell lymphocytes, taking days to occur in patients previously sensitized to the allergen. This is the classic contact dermatitis that appears in 10–48% of the general population. Metal particles cross‐link with proteins and act as antigens initiating an immune response.4

Reports of unexplained persistent pain and loosening after joint replacement caused by hypersensitivity to metal implants were initially published in the mid‐1970s and concerned mostly metal‐on‐metal hip prostheses.58

As in our clinical scenario, if all other common reasons of postoperative complications are excluded, metal hypersensitivity may be a possible predisposing factor that leads to this unexplained clinical picture and possibly to implant failure.

Top three questions

  1. Among patients awaiting TKA, does routine allergy screening, compared to no screening, affect management and/or outcomes?
  2. Among patients with suspected hypersensitivity reaction, does any diagnostic method perform better than others?
  3. Among patients with a confirmed hypersensitivity reaction, which treatment options, compared to others, result in the best outcomes?

Question 1: Among patients awaiting TKA, does routine allergy screening, compared to no screening, affect management and/or outcomes?

Rationale/clinical comment

If routine screening for metal allergy of TKA candidates can identify those at higher risk of developing such hypersensitivity reactions then unwanted reactions leading to socioeconomic burden (prolonged hospitalization, revision surgeries, reduced quality of life, etc.), for an otherwise highly successful intervention, may be prevented.


The only published randomized controlled trial involved 120 patients that were randomized to receive either a seven layer‐coated or noncoated total knee implant and had their plasma ion levels and patch test (PT) assessed preoperatively and at 12 months. This showed that sensitization (positive PT postoperatively) was rare (only 3/120 pts). There was a functional improvement and better quality of life in both groups for all patients. However, those with known metal allergies were excluded from the study since according to local guidelines they could not be randomized.9

Some studies give emphasis to the preoperative history‐taking which, in addition to laboratory testing, can potentially identify patients at risk of metal sensitivity.1013

Niki et al., in their prospective study, suggested that routine prescreening is clinically useful, especially related to Cr sensitivity. In a total of 92 patients, 26% (24 patients) tested positive with lymphocyte transformation test (LTT) preoperatively. An additional five patients developed metal‐related eczema that was relieved fully only in those who had subsequent revision surgery with nonchromium‐containing implants.14

Granchi et al., in two publications, supported that medical history or symptoms of metal allergy prior to implantation seem to be a risk factor for failure. TKA failure was four times more likely in such patients and this was reaffirmed after the systematic review of literature.15,16 Given that many patients with a documented metal allergy on history actually have negative allergy testing, the relationship between the two is somewhat unclear.

Additionally, authors in recently published articles recorded that patient reported allergies (metal and/or environmental exposure, foods, medications, etc.) are associated with significantly decreased functional outcomes and mental health scores after TKA and total hip arthroplasties (THAs) with a follow‐up from one to five years.1719

Conversely, Zeng et al. found no relationship between pain and metal allergy in TKAs or THAs in their study of 87 patients that were pre‐ and postoperatively tested for metal allergy.20

The counterargument is supported by a cohort study of 127 patients, 56 of whom tested positive for metal allergy with the skin PT. This cohort was matched to 161 control TKAs without history or positive laboratory findings. A follow‐up at five years showed no difference in complications, reoperation, or pain.21

Münch et al. from Denmark reported that metal allergy diagnosed preoperatively did not increase the revision surgery in TKAs, after they matched their national knee arthroplasty registry and the national allergy database.22 Additionally, recent reviews have not supported routine testing, and diagnosis should be made when all other possibilities are excluded.4,23

Resolution of clinical scenario

Routine preoperative screening or testing is not clearly supported and opinions vary regarding the appropriate patients to test prior to surgery.

Question 2: Among patients with suspected hypersensitivity reaction, does any diagnostic method perform better than others?

Rationale/clinical importance

As in our previous question, if screening methods can identify potential metal hypersensitive patients awaiting TKA, this will aid toward the best possible and long lasting outcome. On the other hand, postoperative screening may help in the differential diagnosis and provide information valuable toward the next intervention.


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Nov 28, 2021 | Posted by in ORTHOPEDIC | Comments Off on Metal Allergy in Total Knee Arthroplasty

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