No allergic reaction after TKA in a chrome-cobalt-nickel-sensitive patient: case report and review of the literature

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1 Knee Surg Sports Traumatol Arthrosc (2013) 21: DOI /s z KNEE No allergic reaction after TKA in a chrome-cobalt-nickel-sensitive patient: case report and review of the literature Emmanuel Thienpont Yorick Berger Received: 28 September 2011 / Accepted: 29 March 2012 / Published online: 10 April 2012 Ó Springer-Verlag 2012 Abstract Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. Although % of total joint arthroplasty patients develop metal sensitivity, only a few highly susceptible persons (\1 %) exhibit symptoms. We present a case report of a fifty-twoyear-old woman with a preoperatively documented metal allergy who underwent bilateral total knee arthroplasty using a titanium-niobium-coated implant on one side and a chrome-cobalt implant on the other side because of a logistics problem. At 2-year follow-up, no clinical symptoms of allergy or loosening of the implant were observed. Level of evidence IV. Keywords Metal allergy Hypersensitivity Arthroplasty Implant loosening The most common metal sensitizer in humans is nickel followed by cobalt and chromium, while occasional responses have been reported to tantalum, titanium, and vanadium [3, 9 12, 21]. Cross-reactivity between nickel and cobalt is common [4, 9, 11, 12, 18]. Nowadays, three issues are still unknown: the specific metal that mediates implant-related metal hypersensitivity, the true clinical prevalence of metal hypersensitivity (limits and bias of the in vivo dermal patch testing versus in vitro tests), and the clinical impact of metal hypersensitivity on total joint replacement patients [12]. The authors present a case of a chrome-cobalt implant used in a preoperatively documented metal allergy patient without clinical or radiological signs of failure at 2-year follow-up. Introduction All metals in contact with biological systems undergo corrosion [3, 6, 9, 11, 21]. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with native proteins [11, 12]. These organometallic complexes are considered to be candidate antigens/allergens for eliciting metal hypersensitivity responses [6, 11, 12, 16]. This is usually a delayed-type hypersensitivity reaction (DTH) [10, 12, 17]. E. Thienpont (&) Y. Berger Department of Orthopaedic Surgery, Saint Luc University Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium emmanuel.thienpont@uclouvain.be Y. Berger berger.yorick@gmail.com Case report A fifty-two-year-old woman with arthritis of both knees was treated at our institution. She had a left closed wedge high tibial osteotomy 15 years before. In her history, she mentioned atopic dermatitis in contact with metals. Preoperative skin patch testing documented chrome-cobaltnickel allergy. Staged bilateral total knee arthroplasty (TKA) was planned for her within a 6-month interval. First, the left knee was successfully operated using a Vanguard (Biomet, Warsaw, USA) titanium-niobium implant (Fig. 1, right picture). Six months later, the right knee was operated (Fig. 1, left picture). Due to a logistics mistake, a chromecobalt prosthesis instead of the planned titanium-niobium had to be used. During surgery, just before implantation, it was discovered that the wrong side implants were delivered. It was decided not to postpone implantation of chrome-cobalt components, and not to wait for the

2 Knee Surg Sports Traumatol Arthrosc (2013) 21: Fig. 1 Cobalt-chrome knee prosthesis (left side) and titaniumniobium knee prosthesis (right side) after 2- and 2.5-year follow-up titanium-niobium implants to arrive several hours later. At 2-year follow-up, there was no evidence of failure on either side. A Knee Society Score of 98 was obtained. Radiographs show no osteolysis or loosening and a full leg standing alignment on both knees of 5 of valgus. No signs of atopic dermatitis were observed. She is to be reviewed at regular intervals. The patient was informed that data concerning this case would be submitted for publication, and she consented. Review of the literature Allergic reactions can be divided as immediate, which happen within minutes, and are based on a humoral response (Type I-III) or delayed, within hours or days, and are a cell-mediated response (Type IV) [3, 10, 11, 16]. This cell-mediated response is mediated by the T lymphocytes and especially by the CD4-helper cells [6, 11, 12, 20]. This Type IV delayed-type hypersensitivity reaction (DTH) is most common to nickel, chrome, and cobalt [3, 10]. It is also known to happen to titanium and vanadium, but is rather rare in response to polymethyl acrylate (PMMA) [3, 10, 11, 25]. Metal sensitivity in the general population is % [3, 5, 6, 9 11, 13], nickel allergy being the most frequent one (14 %) [9 11]. Female patients are more often sensitive to nickel and males to chromate because of different exposure patterns [2, 21]. In nickel allergy, a cross allergy reaction for chrome or cobalt can be induced [4, 9, 11, 12, 18]. Isolated cobalt allergy is extremely rare [18]. The prevalence of metal sensitivity among patients with well-functioning implants is approximately 25 and 60 % in poorly functioning implants, as measured by dermal patch testing [3, 9 12, 17, 21]. Nickel is especially present in stainless steel, explaining the higher frequency of observed cases in trauma compared to less than 1 % of nickel in chrome-cobalt implants. Stainless steel contains 15 % nickel, 19 % chrome, and 4 % molybdenum. Chrome-cobalt implants contain 1 % nickel, 67 % chrome, 30 % cobalt, and 2 % molybdenum. Finally, titanium alloy components contain 91 % titanium, 5 % aluminum, 3.9 % vanadium, and 0.1 % nickel [9, 11, 14]. Clinical symptoms of allergy are pruritus and itching, redness, and eczema [3, 11, 13, 21]. Definitive criteria for implant allergy will be localized eczema over the knee or the skin incision [13, 17, 25]. Generalized eczema is very rare in total knee arthroplasty because there is no metalmetal contact, and thus, the amount of free metal ions is lower than in metal on metal hips [4, 9]. We should be aware that most of our patients test positive preoperatively for nickel and that it is, however, mostly chrome that induces the eczema [3, 10, 17, 21, 25]. Four criteria have to be fulfilled before being able to confirm the diagnosis of orthopedic dermatitis [9]. The dermatosis has to appear after the implantation of an orthopedic implant. No other etiology can be implicated, and deep infection is excluded [1]. The dermatosis has to be chronic, and finally, the dermatosis has to heal within 2 months after removal of the orthopedic implant [9]. The clinical significance of sensitization to implanted metals has long since been a matter of debate [3, 8, 11, 15, 16, 23]. Some studies have shown that sensitization to metal implants is prevalent, while others refute these data and concluded that hypersensitivity fails to develop or even that hypersensitive patients become desensitized after implantation [3, 4, 17]. An induction of metal tolerance and T-cell reduction has been described [11], if it was not initially a false positive test of course [19]. Metal hypersensitivity might be merely a clinical curiosity except for known over-aggressive immune responses to haptenic antigens [11]. A big issue in diagnosing orthopedic implant allergy is that there is no universally accepted diagnostic test and what is the validity of positive skin tests compared to deep peri-implant tissue reactions [4, 8, 10, 19]. There are in vitro and in vivo metal allergy tests [11, 17, 24]. The in vitro tests are either a lymphocyte transformation test (LTT), which measures the proliferative response of lymphocytes following activation, or leukocyte migration inhibition testing (LIF or MIF), which measures the limitation in migration of the leukocytes [11, 17]. For the lymphocyte transformation test, a radioactive marker is added to lymphocytes along with the desired challenge agent. After 6 days, the proliferation factor or stimulation index is calculated by using measured radiation counts per minute. The main disadvantage of this test is the

3 638 Knee Surg Sports Traumatol Arthrosc (2013) 21: need for a specialized lab and the high cost of these tests [11]. Several reports indicate that LTT is better suited for testing of implant-related sensitivity [11]. The leukocyte inhibition test detects lymphokine MIF, which acts to prevent lymphocytes from leaving a site where foreign antigens are present, and thus indicates an active immune response and metal sensitivity. The test is performed by obtaining a blood sample and isolating the lymphocytes, which are then mixed with solutions of nickel, chromium, cobalt, or titanium. The test is positive if the lymphocytes do not migrate away from the dissolved metal [11, 16]. A positive leukocyte inhibition test is well correlated with pain, swelling, and dermatological reactions [11]. This test becomes negative after removal of the implant, contrary to skin patch tests [19, 24]. Because of the complexity of these in vitro tests, easy in vivo epicutaneous tests (patch tests) were developed [10, 11, 19]. They are cheap, suitable for larger-scale screening and allow the simultaneous evaluation of all immunogenic substances [10, 11, 17, 19]. There is, however, continuing concern about the applicability of skin testing to the study of immune responses to implants [11, 24]. Sensitization to a hapten will be related to the status of the implant. In patients without an implant, % test was positive on skin patch testing. In the presence of a stable implant, 48 % test was positive, and 60 % test was positive after loosening of the prosthesis [10]. The most frequent hapten will clearly be nickel with 10 % of sensitization, followed by most other metals like chromium (5 %), cobalt (5 %), manganese (5 %), titanium (5 %), and vanadium (5 %) [10, 11, 18]. Niobium chloride has never been found positive until now [10]. To date, no standardized titanium preparations exist for patch testing [14, 19, 21]. Skin patch testing has a very high sensitivity (100 %) but a lower specificity (64 %). So the diagnostic value of a skin patch test lies in a negative test. A positive patch test cannot predict failure; however, one study showed that in patients with a positive medical history for metal DTH, a positive skin patch would be highly predictive for knee failure with a positive likelihood ratio of 4 [10]. A positive result is not indicative of a true hypersensitivity and must be considered in the clinical context [8, 9]. The clinical significance of the allergy remains controversial [17]. The causes of these skin immunologic reactions are unclear [3, 9]. It is thought that antigen-presenting cells that are localized to the skin (dendrite cells and dermal Langerhans cells) may handle antigens differently than the antigen-presenting cells that are systemic (macrophages and monocytes) [6, 11, 12]. Therefore, patients with positive skin tests may never develop any implant reactivity or skin tests may not return to normal after removal of the implant [9, 17, 19]. Finally, we need to be aware that we can induce hypersensitivity by extended dermal contact during patch testing [11, 17, 19]. An important factor to consider in sensitization is metal ion exposure and release [7, 11]. Implants from different manufacturers have varying metal compositions, but the nature of the alloy and the local exposure are also important [11, 17]. Plasma spray coatings limit exposure where roughened surfaces increase the available area for ion release [17]. Therefore, titanium implants are coated through physical vapor deposition with niobium nitrate to limit the possible release of the 0.1 % of nickel [14], because it is well-known that the exposure of nickel-containing titanium in an acidic environment will provoke nickel release [21]. Depending on the alloy, release of nickel ions could create implant problems with loosening, and in a subgroup of patients, release of chrome would create eczema and skin problems [3, 15 17, 20, 21, 24, 25]. Some authors have stated that cemented metal-to-plastic joint prosthesis is safe, even in case of pre-existing metal allergy [4, 11, 15, 23]. In case of eczema after total knee arthroplasty, a local dermatologic treatment can be proposed. If this treatment should not be satisfactory, the allergenic implant should be removed and revision with an oxidized zirconium Zr-2.5Nb alloy (Oxinium, Smith & Nephew) or a titanium-niobium (Biomet or Stryker) prosthesis should be performed [5, 7, 9, 13, 17]. To make it even more controversial, we have to remember that titanium components contain impurities like nickel [14, 21] and that allergy to titanium has been described too [11, 21]. So using Oxinium components for the femoral component only, in the presence of a titanium tibial tray or an extension stem, could make little sense on the allergy side, but still successful cases have been published [5, 9, 22]. Discussion The most important finding of this case report was that good clinical and radiological results were obtained on both knees. However, in this one patient, on one side chrome-cobalt components were used despite a history of metal allergy and positive skin testing prior to the surgery. One of the major difficulties in understanding the clinical implications of hypersensitivity to implant components is the lack of universally accepted testing methods [10, 15, 17]. No consensus has yet been reached as to whether skin patch or in vitro testing is necessary [10, 11]. Because of the practical side, epicutaneous skin testing is the most common for the moment, but there are still a lot of doubts

4 Knee Surg Sports Traumatol Arthrosc (2013) 21: about its validity in determining a deep-tissue hypersensitivity [10, 17]. Patch testing has a sensitivity value of one [10, 13, 19]. Its negative predictive value is probably the most valuable [10]. The probability of having a metal sensitization in the presence of a negative patch test is null [10]. There is a lack of knowledge of the association between dermal and deep implant sensitivity [9 11, 17]. Even patients with known metal allergy often do not react to their metal prosthesis [9]. Another limitation in establishing the role of the sensitivity to implant components is the paucity of clinical studies providing clear data of a connection between metal sensitivity and the outcome of the implant [10, 15, 23]. The frequency of positive skin reactions increased significantly after TKA, but the clinical impact of this event on the implant failure has not been proven, because no significant differences were found between stable and loosened prostheses [10, 17, 23]. Granchi et al. [10] found that there was a risk in patients who had symptoms of metal hypersensitivity before the implantation, which negatively influenced the implant life span and increased fourfold the likelihood to have a TKA failure. However, the large confidence interval did not completely validate the predictive value (likelihood ratio: 4.02; 95 % CI = ) [10]. In vitro tests are becoming more available and suggest being more sensitive and easier to correlate with the clinical implant situation [11]. Clinical symptoms like atopic dermatitis (eczema) are rare and are related to chrome sensitivity [3, 9, 10, 17]. Loosening of implants could be related to nickel allergy, and probably only in a subgroup [20]. Sensitization occurs in genetically predisposed subjects [11, 22]. Positive skin tests suggest the susceptibility of the patient [17, 20]. A history of reaction to jewelry or metallic devices can be an important sign [2, 11, 19]. At this time, there is no evidence that there is an increased risk of a reaction to an implanted device in patients who have skin patch sensitivity but no history of reaction to metallic materials [3, 11, 24]. In cases of proven orthopedic dermatitis, good results were obtained by revision with non-chromium-containing components [5, 10]. Since zirconium and titanium-niobium primary implants are available on the shelf, it might be wise to use these in patients that mention the problem preoperatively and where the supposed metal allergy cannot be excluded by a negative skin test [8, 9, 17, 19]. Conclusion There is no knowledge about the association of dermal and deep implant sensitivity, and even patients with known metal allergy often do not react to their implant [8, 10]. Metal sensitivity to implants may exist as an extreme complication in only a few highly predisposed people [9 12, 17], but it may also be a subtle contributor to implant failure [11]. The degree to which a known metal hypersensitivity may elicit an overaggressive immune response remains unpredictable [11, 17]. References 1. Anand A, McGlynn F, Jiranek W (2009) Metal hypersensitivity: can it mimic infection? J Arthroplasty 24(826):e25 e28 2. Basketter DA, Briatico-Vangosa G, Kaestner W, Lally C, Bontinck WJ (1993) Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis? Contact Dermat 28: Basko-Plluska JL, Thyssen JP, Schalock PC (2011) Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis 22: Beecker J, Gordon J, Pratt M (2009) An interesting case of joint prosthesis allergy. Dermatitis 20: Bergschmidt P, Bader R, Mittelmeier W (2012) Metal hypersensitivity in total knee arthroplasty: revision surgery using a ceramic femoral component: a case report. Knee 19: Caicedo MS, Desai R, McAllister K, Reddy A, Jacobs JJ, Hallab NJ (2009) Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasone danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J Orthop Res 27: Cousen PJ, Gawkrodger DJ (2012) Metal allergy and secondgeneration metal-on-metal arthroplasties. Contact Dermat 66: Frigerio E, Pigatto PD, Guzzi G, Altomare G (2011) Metal sensitivity in patients with orthopedic implants: a prospective study. Contact Dermat 64: Gao X, Rx He, Yan SG, Wu LD (2011) Dermatitis associated with chromium following total knee arthroplasty. J Arthroplasty 26(665):e13 e Granchi D, Cenni E, Tigani D, Trisolino G, Baldini N, Giunti A (2008) Sensitivity to implant materials in patients with total knee arthroplasties. Biomaterials 29: Hallab N, Merritt K, Jacobs JJ (2001) Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg Am 83: Hallab NJ, Caicedo M, Epstein R, McAllister K, Jacobs JJ (2010) In vitro reactivity to implant metals demonstrates a persondependant association with both T-cell and B-cell activation. J Biomed Mat Res 92(2): Handa S, Dogra S, Prasad R (2003) Metal sensitivity in a patient with a total knee replacement. Contact Dermat 49: Harloff T, Hönle W, Holzwarth U, Bader R, Thomas P, Schuh A (2010) Titanium allergy or not? Impurity of titanium implants. Materials 2: Jacobs JJ, Hallab NJ (2006) Loosening and osteolysis associated with metal-on-metal bearings: a local effect of metal hypersensitivity? J Bone Joint Surg Am 88: Merritt K, Rodrigo JJ (1996) Immune response to synthetic materials. Sensitization of patients receiving orthopaedic implants. Clin Orthop Relat Res 326: Niki Y, Matsumoto H, Otani T, Yatabe T, Kondo M, Yoshimine F, Toyama Y (2005) Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials 26:

5 640 Knee Surg Sports Traumatol Arthrosc (2013) 21: Perumal V, Alkire M, Swank ML (2010) Unusual presentation of cobalt hypersensitivity in a patient with a metal on metal arthroplasty. Am J Ortoped 39:e39 e Schalock PC, Menné T, Johansen JD, Taylor JS, Malbach HI, Lidén C, Bruze M, Thyssen JP (2012) Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use. Contact Dermat 66: Summer B, Paul C, Mazoochian F, Rau C, Thomsen M, Banke I, Gollwitzer H, Dietrich KA, Mayer-Wagner S, Ruzicka T, Thomas P (2010) Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni. Contact Dermat 63: Thomas P, Thomas M, Summer B, Dietrich K, Zauzig M, Steinhauser E, Krenn V, Arnholdt H, Flaig M (2011) Impaired wound-healing, local eczema, and chronic inflammation following titanium osteosynthesis in a nickel and cobalt-allergic patient. A case report and review of the literature. J Bone Joint Surg Am 93:e Thomsen M, Rozak M, Thomas P (2011) Pain in a chromiumallergic patient with total knee arthroplasty: disappearance of symptoms after revision with a special surface-coated TKA- A case report. Acta Orthop 82: Thyssen JP, Jakobsen SS, Engkilde K, Johansen JD, Soballe K, Menne T (2009) The association between metal allergy, total hip arthroplasty, and revision. Acta Orthop 80: Thyssen JP, Menné T, Schalock PC, Taylor JS, Maibach HI (2011) Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic orthopaedic implants before and after surgery. Br J Dermatol 164: Verma SB, Mody B, Gawkrodger DJ (2006) Dermatitis on the knee following knee replacement: a minority of cases show contact allergy to chromate, cobalt or nickel but a causal association is unproven. Contact Dermat 54: