Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty

Abstract

Metal sensitivity (MS) reactions to implant metals represent a rare but well-documented complication following total joint arthroplasty (TJA). Although 20–25% of post-TJA patients develop MS, only a few highly susceptible patients (<1%) exhibit symptoms. Whether surgeons should perform screening for MS is currently a matter of debate. The present study investigated the clinical importance of screening for patients predisposed to symptomatic MS, and the specific metals causing symptomatic MS following total knee arthroplasty (TKA). Between 2000 and 2002, a total of 108 primary TKAs were performed on 92 patients. Preoperatively, all patients underwent modified lymphocyte stimulation test (mLST) to Ni, Co, Cr, and Fe. Of the 92 patients, 24 (26%) displayed positive preoperative responses to at least one metal. Five patients displayed implant metal-related eczema and were all mLST-positive preoperatively, suggesting that screening for symptomatic MS is clinically useful. Two of these underwent revision TKA and thereafter, eczema healed and mLST results changed from positive to negative. All mLST-positive patients were divided into three groups: Group I, patients with eczema; Group II, patients with clear history of MS; and Group III, patients neither eczema nor history of MS. When the type of sensitive metals were compared among the three groups, a significant association between presence of Cr-sensitivity and development of eczema (P<0.05) was identified. No significant association was observed between other metals and development of eczema or history of MS. This indicates that Cr is a potential candidate metal for causing eczema in our TKA series, and Cr-sensitivity may offer a potential predictor for symptomatic MS. The present study indicates that the surgeons should undertake routine preoperative screening for MS, particularly to Cr.

Introduction

Recently, total joint arthroplasty (TJA) has become a common and quite successful procedure, and its resultant complications are now being seen in much greater numbers. Biological reactions to implant constituents have recently gained attention as a causative factor for loosening of the prosthetic implant. These biological reactions are known to be mediated by three distinct mechanisms: hypersensitivity to ionic metals; foreign body reactions to wear particles [1], [2], [3], [4], [5]; and reactions to metal corrosion products [6], [7], [8], [9]. Biomaterial-related metal sensitivity (MS) has been implicated in type-IV delayed-type hypersensitivity reactions mediated by antigen-presenting cells and T lymphocytes [10], [11]. Historically, this has been examined in vivo using the skin patch test [12], [13], [14] and in vitro using the lymphocyte stimulation test (LST) [15], [16], [17] and leukocyte migration inhibition test [18]. Among these tests, patch tests are now the most common method of diagnosing MS, due to the advantages of cost and technical simplicity. However, several problems remain unresolved in this test: dermal contact of aqueous metal solutions is likely to different substantially from exposure to metal ions in a closed periprosthetic environment; patch test is likely to overpredict MS in screening tests, and more people are diagnosed as allergic than will actually react to implants; and MS may be induced in previously nonsensitive patients by patch test itself. In vitro tests, such as LST and leukocyte migration inhibition test, are thus more reliable than patch tests, and LST was adopted as a screening test for MS in the present study.

Prevalence of MS among patients who have undergone TJA has been shown to be approximately 20–25%, which is 10% higher than that in the general population or patients about to undergo TJA [19], [20], [21]. This difference in prevalence is considered responsible for the development of implant-induced sensitization after TJA [22]. The presence of implant-induced sensitization has raised concern as to whether it is clinically useful to screen for metal-sensitized patients preoperatively, and whether surgeons should screen for MS preoperatively.

Despite substantial prevalence of MS before and after TJA, symptomatic MS presenting after TJA as cutaneous complications, such as eczematous dermatitis, is rare and is currently estimated to occur in less than 1% of patients [23]. This indicates that conventional test methods for screening MS do not represent suitable predictors of onset of symptomatic MS. In fact, determining the degree to which a known condition of MS may elicit an overaggressive immune response on the skin is difficult. This unreliable diagnosis by conventional tests is partly attributable to the involvement of nonimmunological responses to metals mediated by metal ion-derived activated oxygen species (AOS) [7], [9]. The modified lymphocyte stimulation test (mLST) has been established in our laboratory to determine precise lymphocyte reactivity to metals in vitro using anti-HLA class II antibody [24]. The purpose of this study was to investigate the clinical importance of screening for patients predisposed to symptomatic MS using mLST. In addition, we also investigated specific metals causing symptomatic MS following total knee arthroplasty (TKA).