Metal sensitivity/allergy

A recent comment on another blog posting requested information on metal allergy/sensitivity. While this is a rare situation, I do have first-hand experience dealing with it. Common orthopedic materials include: cobalt, chrome, nickel, titanium, zirconium, polyethylene, and polymethylmethacrylate. Reactions have been reported to each of these materials. Thankfully these reactions are rare. 

In the unusual case of a poorly functioning joint replacement, it is crucial to rule out other sources of dissatisfaction or failure prior to considering allergic reaction to the implant materials. More common issues include: infection, loosening, malalignment, instability, or wear. 

If a patient has a known sensitivity to any material, it is important to let your surgeon know this PRIOR to the intended surgery. It is reasonable to consider preoperative material testing in such situations. 

Once implanted, if sensitivity or allergy is felt to the the issue, revision surgery will be required. Depending on the particular material sensitivity, very specific implants will be required. I actually had to resort to using a custom zirconium revision total knee system in one case for a patient who was found to have intolerance to both nickel and titanium. 

Metal sensitivity is a controversial topic, however, and the literature continues to develop. It appears that after implantation of orthopedic devices, more people will test positive for sensitivity. In the case of positive metal sensitivity tests in association with a poorly functioning implant, it is unclear if the sensitivity is a cause of the implant difficulty or a result. 


Below, I have attached some recent abstracts highlighting some important points. 



Int J Surg Case Rep. 2018 Jun 23;49:110-114. doi: 10.1016/j.ijscr.2018.06.011. [Epub ahead of print] Hypersensitivity to orthopaedic implant manifested as erythroderma: Timing of implant removal. Phedy P(1), Djaja YP(2), Boedijono DR(3), Wahyudi M(4), Silitonga J(5), Solichin I(6). Author information: (1)Department of Orthopaedic and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia. Electronic address: phedy.phe@gmail.com. (2)Department of Orthopaedic and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia. Electronic address: yoshipratamadjaja@yahoo.com. (3)Department of Orthopaedic and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia. Electronic address: drboedijono@gmail.com. (4)Department of Orthopaedic and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia. Electronic address: dr.m.wahyudi@gmail.com. (5)Department of Orthopaedic and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia. Electronic address: jamot_silitonga@yahoo.com. (6)Rumah Sakit Orthopaedi Purwokerto, Purwokerto, Indonesia. Electronic address: rsop4all@rsop.co.id. INTRODUCTION: Incidence of hypersensitivity to orthopaedic implant, once estimated in less than 1% of population, recently has increased to 10%. Controversies about the timing of implant removal remain, especially due to the fact that implant hypersensitivity may be a contributing factor to implant failure. We present a case report and literature reviews to establish the decision making for the timing of implant removal in the presence of implant hypersensitivity. PRESENTATION OF CASE: Female, 42 years old with nonunion of mid-shaft tibia and fibula which was treated with ORIF with conventional SAE16 stainless steel plate and bone graft. A week after, she developed a generalized rash, which is later diagnosed as erythroderma, that relapsed despite adequate systemic corticosteroid. Poor healing of surgical site wound were marked. After the implant removal, the cutaneous condition improved and no relapse were found. DISCUSSION: Management of hypersensitivity to implants involved corticosteroid administration, removal or replacement of implants, or implants coating with polytetrafluoroethylene. ​Currently there are no specific guidelines regulating the management of implant allergy based on the timing of the onset, especially in fracture cases. The decision-making would be straightforward if union was already achieved. Otherwise, controversies would still occur. In this paper, we proposed an algorithm regarding the steps in managing metal allergy due to implant in fracture cases. CONCLUSION: Despite the concerns regarding implant survival in hypersensitivity cases, the decision whether the implant should be removed or replaced should be based on the time and condition of the fracture healing process. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.ijscr.2018.06.011 PMCID: PMC6037004 PMID: 30005360

J Clin Orthop Trauma. 2018 Jan-Mar;9(1):3-6. doi: 10.1016/j.jcot.2017.10.003. Epub 2017 Oct 10. Metal hypersensitivity in total hip and knee arthroplasty: Current concepts. Akil S(1), Newman JM(1), Shah NV(1), Ahmed N(2), Deshmukh AJ(3), Maheshwari AV(1). Author information: (1)Department of Orthopaedic Surgery, State University of New York (SUNY), Downstate Medical Center, Brooklyn, NY, USA. (2)Saba University School of Medicine, Saba, Caribbean Netherlands, Netherlands. (3)Department of Orthopaedic Surgery, NYU Langone Medical Center, VA New York Harbor Healthcare System, New York, NY, USA. Metal hypersensitivity (MHS) is a rare complication of total joint arthroplasty that has been linked to prosthetic device failure when other potential causes have been ruled out. The purpose of this review was to conduct an analysis of existing literature in order to get a better understanding of the pathophysiology, presentation, diagnosis, and management of MHS. It has been described as a type IV hypersensitivity reaction to the metals comprising prosthetic implants, often nickel and cobalt-chromium. Patients suffering from this condition have reported periprosthetic joint pain and swelling as well as cutaneous, eczematous dermatitis. There is no standard for diagnosis MHS, but tests such as patch testing and lymphocyte transformation testing have demonstrated utility, among others. Treatment options that have demonstrated success include administration of steroids and revision surgery, in which the existing metal implant is replaced with one of less allergenic materials. Moreover, the definitive resolution of symptoms has most commonly required revision surgery with the use of different implants. However, more studies are needed in order to understand the complexity of this subject. DOI: 10.1016/j.jcot.2017.10.003 PMCID: PMC5884053 [Available on 2019-01-01] PMID: 29628676

J Am Acad Orthop Surg. 2017 Oct;25(10):693-702. doi: 10.5435/JAAOS-D-16-00007. Allergic or Hypersensitivity Reactions to Orthopaedic Implants. Roberts TT(1), Haines CM, Uhl RL. Author information: (1)From the Neurological Institute, Cleveland Clinic, Cleveland, OH (Dr. Roberts and Dr. Haines) and the Division of Orthopaedic Surgery, Albany Medical Center, Albany, NY (Dr. Uhl). Allergic or hypersensitivity reactions to orthopaedic implants can pose diagnostic and therapeutic challenges. Although 10% to 15% of the population exhibits cutaneous sensitivity to metals, deep-tissue reactions to metal implants are comparatively rare. Nevertheless, the link between cutaneous sensitivity and clinically relevant deep-tissue reactions is unclear. Most reactions to orthopaedic devices are type IV, or delayed-type hypersensitivity reactions. The most commonly implicated allergens are nickel, cobalt, and chromium; however, reactions to nonmetal compounds, such as polymethyl methacrylate, antibiotic spacers, and suture materials, have also been reported. Symptoms of hypersensitivity to implants are nonspecific and include pain, swelling, stiffness, and localized skin reactions. Following arthroplasty, internal fixation, or implantation of similarly allergenic devices, the persistence or early reappearance of inflammatory symptoms should raise suspicions for hypersensitivity. However, hypersensitivity is a diagnosis of exclusion. Infection, as well as aseptic loosening, particulate synovitis, instability, and other causes of failure must first be eliminated. DOI: 10.5435/JAAOS-D-16-00007 PMID: 28953084 [Indexed for MEDLINE]

Rheumatol Ther. 2017 Jun;4(1):45-56. doi: 10.1007/s40744-017-0062-6. Epub 2017 Mar 31. Hypersensitivity to Orthopedic Implants: A Review of the Literature. Wawrzynski J(1), Gil JA(2), Goodman AD(3), Waryasz GR(3). Author information: (1)Warren Alpert Medical School, Brown University, Providence, RI, USA. (2)Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA. joseph_gil@brown.edu. (3)Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA. Awareness of rare etiologies for implant failure is becoming increasingly important. In addition to the overall increase in joint arthroplasties, revision surgeries are projected to increase dramatically in the coming years, with volume increasing up to seven-fold between 2005 and 2030. The literature regarding the relationship between metal allergy and implant failure is controversial. It has proven difficult to determine whether sensitization is a cause or a consequence of implant failure. Testing patients with functional implants is not a clinically useful approach, as the rate of hypersensitivity is higher in implant recipients than in the general population, regardless of the status of the implant. As a result of the ineffectiveness of preoperative patch testing for predicting adverse outcomes, as well as the high cost of implementing such patch testing as standard procedure, most orthopedists and dermatologists agree that an alternative prosthesis should only be considered for patients with a history of allergy to a metal in the standard implant. In patients with a failed implant requiring revision surgery, hypersensitivity to an implant component should be considered in the differential diagnosis. Because a metal allergy to implant components is currently not commonly considered in the differential for joint failure in the orthopedic literature, there should be improved communication and collaboration between orthopedists and dermatologists when evaluating joint replacement patients with a presentation suggestive of allergy. DOI: 10.1007/s40744-017-0062-6 PMCID: PMC5443731 PMID: 28364382

HSS J. 2017 Feb;13(1):12-19. doi: 10.1007/s11420-016-9514-8. Epub 2016 Jul 22. Allergy in Total Knee Replacement. Does It Exist?: Review Article. Faschingbauer M(1)(2), Renner L(1)(3), Boettner F(1). Author information: (1)Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA. (2)Department of Orthopaedic Surgery, University of Ulm, RKU, Oberer Eselsberg 45, 89081 Ulm, Germany. (3)Department of Orthopedic Surgery, Charite Universitaetsmedizin, Center for Musculosceletal Surgery, Chariteplatz 1, 10117 Berlin, Germany. BACKGROUND: There is little data on whether preexisting allergies to implant materials and bone cement have an impact on the outcome of TKA. QUESTIONS/PURPOSES: This review article analyzes the current literature to evaluate the prevalence and importance of metal and cement allergies for patients undergoing total knee arthroplasty. METHODS: A review of the literature was performed using the following search criteria: "knee," "arthroplasty," and "allergy" as well as "knee," "arthroplasty," and "hypersensitivity." RESULTS: One hundred sixteen articles were identified on PubMed, Seventy articles could be excluded by reviewing the title and abstract leaving 46 articles to be included for this review. The majority of the studies cited patch testing as the gold standard for screening and diagnosis of hypersensitivity following TKA. There is consensus that patients with self-reported allergies against metals or bone cement and positive patch test should be treated with hypoallergenic materials or cementless TKA. Treatment options include the following: coated titanium or cobalt-chromium implants, ceramic, or zirconium oxide implants. CONCLUSION: Allergies against implant materials and bone cement are rare. Patch testing is recommended for patients with self-reported allergies. The use of special implants is recommended for patients with a confirmed allergy. DOI: 10.1007/s11420-016-9514-8 PMCID: PMC5264571 PMID: 28167868 Conflict of interest statement: Martin Faschingbauer, MD reports other from Deutsche Forschungsgemeinschaft, during the conduct of the study. Lisa Renner, MD has declared that she has no conflict of interest. Friedrich Boettner, MD reports personal fees from Smith & Nephew, during the conduct of the study; personal fees from Ortho Development, outside the work. Human/Animal Rights This article does not contain any studies with human or animal subjects performed by the any of the authors. Informed Consent N/A Required Author Forms Disclosure forms provided by the authors are available with the online version of this article.

Knee Surg Relat Res. 2016 Dec 1;28(4):312-318. doi: 10.5792/ksrr.16.018. Availability of Total Knee Arthroplasty Implants for Metal Hypersensitivity Patients. Ajwani SH(1), Charalambous CP(1)(2)(3). Author information: (1)Department of Orthopaedics, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UK. (2)School of Medicine and Dentistry, University of Central Lancashire, Preston, UK. (3)Institute of Inflammation and Repair, School of Medical and Human Sciences, University of Manchester, Manchester, UK. Purpose: To provide information on the type of "hypersensitivity-friendly" components available for primary total knee arthroplasty (TKA) in the current market. Materials and Methods: Implant manufactures were identified using the 2013 National Joint Registries of the United Kingdom and Sweden and contacted to obtain information about the products they offer for patients with metal hypersensitivity. Results: Information on 23 TKA systems was provided by 13 implant manufacturers. Of these, 15 systems had options suitable for metal hypersensitivity patients. Two types of "hypersensitivity-friendly" components were identified: 10 implants were cobalt chrome prostheses with a "hypersensitivity-friendly" outer coating and 5 implants were made entirely from non-cobalt chrome alloys. Conclusions: The results of this study suggest that several hypersensitivity TKA options exist, some of which provide the same designs and surgical techniques as the conventional implants. The information in this study can guide TKA surgeons in making informed choices about implants and identifying implants that could be examined in future controlled studies comparing outcomes between "hypersensitivity-friendly" and conventional implants. DOI: 10.5792/ksrr.16.018 PMCID: PMC5134788 PMID: 27894179

J Am Acad Orthop Surg. 2016 Feb;24(2):106-12. doi: 10.5435/JAAOS-D-14-00290. Metal Hypersensitivity and Total Knee Arthroplasty. Lachiewicz PF(1), Watters TS, Jacobs JJ. Author information: (1)From the Department of Orthopaedic Surgery, Duke University Medical Center (Dr. Lachiewicz and Dr. Watters) and the Durham Veterans Administration Medical Center (Dr. Lachiewicz), Durham, NC, and the Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL (Dr. Jacobs). Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Some reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted. DOI: 10.5435/JAAOS-D-14-00290 PMCID: PMC4726476 PMID: 26752739 [Indexed for MEDLINE]

Biomed Res Int. 2015;2015:137287. doi: 10.1155/2015/137287. Epub 2015 Mar 25. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty. Mitchelson AJ(1), Wilson CJ(1), Mihalko WM(2), Grupp TM(3), Manning BT(1), Dennis DA(4), Goodman SB(5), Tzeng TH(1), Vasdev S(1), Saleh KJ(1). Author information: (1)Division of Orthopaedics and Rehabilitation, Department of Surgery, Southern Illinois University School of Medicine, P.O. Box 19679, Springfield, IL 62794-9679, USA. (2)Department of Orthopaedic Surgery & Biomedical Engineering, University of Tennessee, Memphis, TN 38017, USA. (3)Clinic for Orthopaedic Surgery, Campus Grosshadern, Ludwig Maximilians University, 80539 Munich, Germany ; Aesculap AG, Research & Development, 78532 Tuttlingen, Germany. (4)Colorado Joint Replacement, Denver, CO 80210, USA. (5)Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, CA 94063, USA. The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. DOI: 10.1155/2015/137287 PMCID: PMC4390183 PMID: 25883940 [Indexed for MEDLINE]

Acta Orthop. 2015 Jun;86(3):378-83. doi: 10.3109/17453674.2014.999614. Epub 2015 Jan 13. The association between metal allergy, total knee arthroplasty, and revision: study based on the Danish Knee Arthroplasty Register. Münch HJ(1), Jacobsen SS, Olesen JT, Menné T, Søballe K, Johansen JD, Thyssen JP. Author information: (1)National Allergy Research Centre, Department of Dermatology and Allergology , Gentofte University Hospital , Hellerup. BACKGROUND AND PURPOSE: It is unclear whether delayed-type hypersensitivity reactions against implanted metals play a role in the etiopathogenesis of malfunctioning total knee arthroplasties. We therefore evaluated the association between metal allergy, defined as a positive patch test reaction to common metal allergens, and revision surgery in patients who underwent knee arthroplasty. PATIENTS AND METHODS: The nationwide Danish Knee Arthroplasty Register, including all knee-implanted patients and revisions in Denmark after 1997 (n = 46,407), was crosslinked with a contact allergy patch test database from the greater Copenhagen area (n = 27,020). RESULTS: 327 patients were registered in both databases. The prevalence of contact allergy to nickel, chromium, and cobalt was comparable in patients with and without revision surgery. However, in patients with 2 or more episodes of revision surgery, the prevalence of cobalt and chromium allergy was markedly higher. Metal allergy that was diagnosed before implant surgery appeared not to increase the risk of implant failure and revision surgery. INTERPRETATION: While we could not confirm that a positive patch test reaction to common metals is associated with complications and revision surgery after knee arthroplasty, metal allergy may be a contributor to the multifactorial pathogenesis of implant failure in some cases. In cases with multiple revisions, cobalt and chromium allergies appear to be more frequent. DOI: 10.3109/17453674.2014.999614 PMCID: PMC4443448 PMID: 25582229 [Indexed for MEDLINE]

J Long Term Eff Med Implants. 2014;24(1):37-44. Metal sensitivities among TJA patients with post-operative pain: indications for multi-metal LTT testing. Caicedo MS(1), Solver E(2), Coleman L(2), Hallab NJ(3). Author information: (1)Orthopedic Analysis, LLC, Chicago, IL 60612; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612. (2)Orthopedic Analysis, LLC, Chicago, IL 60612. (3)Orthopedic Analysis, LLC, Department of Immunology, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612. Metal sensitivity testing is generally the diagnosis method of last resort for aseptic painful implants with elevated inflammatory responses. However, the relationship between implant-related pain and implant-debris-related metal sensitization remains incompletely understood. Although a sensitivity to nickel alone has been used as a general measure of metal allergy, it may lack the specificity to correlate sensitivity to specific implant metals and thus to select a biologically appropriate implant material. In this retrospective study, we report the incidence of pain and nickel sensitivity in patients with total joint arthroplasties (TJAs) referred for metal sensitivity testing (n=2018). We also correlated the degree of nickel hypersensitivity to implant pain levels (none, mild, moderate, and high, using a scale of 0-10) and the incidence of sensitivity to alternative implant metals in highly nickel-reactive subjects. Most patients (>79%) reported pain levels that were moderate to high regardless of implant age, whereas patients with severely painful TJAs had a statistically greater incidence of nickel sensitivity over the short-term post-operative period (≤4 years). Patients with moderate pain scores (4-7) and high pain scores (≥8) also exhibited significantly higher sensitivity to nickel compared to patients with no pain and no implant (controls) (p<0.05). Highly nickel-sensitive subjects (SI>8) also showed incidences of sensitization to alternative materials such as cobalt, chromium, or molybdenum (57%) or aluminum or vanadium alloy (52%). These data suggest that painful TJAs caused by metal sensitivity more likely occur relatively early in the post-operative period (≤4 years). The incidences of sensitivity to alternative implant metals in only a subset of nickel-reactive patients highlights the importance of testing for sensitization to all potential revision implant materials. PMID: 24941404 [Indexed for MEDLINE]

J Long Term Eff Med Implants. 2014;24(1):25-36. Evaluation and management of metal hypersensitivity in total joint arthroplasty: a systematic review. Amini M(1), Mayes WH(1), Tzeng A(2), Tzeng TH(3), Saleh KJ(3), Mihalko WM(4). Author information: (1)Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center; Campbell Clinic Orthopaedics, Memphis, TN. (2)Koch Institute for Integrative Cancer Research, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA. (3)Department of Orthopaedic Surgery, Southern Illinois University School of Medicine, Springfield, IL. (4)Campbell Clinic Department of Orthopaedics & Biomedical Engineering University of Tennessee Health Science Center, TN, USA. Metal hypersensitivity has been an identified problem in orthopedics for nearly half a century, but its implications remain unclear. Establishing which total joint arthroplasty (TJA) candidates may do poorly with conventional implants and which patients would benefit from revision to an allergen-free implant remains challenging. Our systematic search of the MEDLINE database identified 52 articles for inclusion in our review. Case reports revealed that half of patients presented with pain and swelling, while only one-third presented with cutaneous symptoms. All patients were symptomatic within the first post-operative year; 90% were symptomatic within 3 months. Reports of patch testing revealed that patients with TJAs were positive for metal sensitivity more often than patients without TJAs (OR 1.3). Those with poorly functioning arthroplasties and those who had already had revisions tested positive more often than those with well-functioning TJAs (OR 1.7) and those without TJAs (OR 3.1). Lymphocyte transformation testing (LTT) shows promise in diagnosing metal allergy, and components of bone cement are also being recognized as potential allergens. Further work is necessary to delineate which patients should be tested for metal allergy and which patients would benefit from allergen-free implants. PMID: 24941403 [Indexed for MEDLINE]

Ann Allergy Asthma Immunol. 2014 Aug;113(2):131-6. doi: 10.1016/j.anai.2014.05.012. Epub 2014 Jun 13. Metal hypersensitivity in total joint arthroplasty. Pinson ML(1), Coop CA(2), Webb CN(2). Author information: (1)Department of Medicine, Allergy/Immunology Division, Wilford Hall Ambulatory Surgical Center, San Antonio, Texas. Electronic address: michelle.pinson.1@us.af.mil. (2)Department of Medicine, Allergy/Immunology Division, Wilford Hall Ambulatory Surgical Center, San Antonio, Texas. OBJECTIVE: To review the clinical manifestations, testing methods, and treatment options for hypersensitivity reactions to total joint arthroplasty procedures. DATA SOURCES: Studies were identified using MEDLINE and reference lists of key articles. STUDY SELECTIONS: Randomized controlled trials were selected when available. Systematic reviews and meta-analyses of peer-reviewed literature were included, as were case series and observational studies of clinical interest. RESULTS: Total joint arthroplasty procedures are increasing, as are the hypersensitivity reactions to these implants. Evidence is not conclusive as to whether metal joint implants increase metal sensitivity or whether metal sensitivity leads to prosthesis failure. Currently, patch testing is still the most widely used method for determining metal hypersensitivity; however, there are no standardized commercial panels specific for total joint replacements available currently. In vitro testing has shown comparable results in some studies, but its use in the clinical setting may be limited by the cost and need for specialized laboratories. Hypersensitivity testing is generally recommended before surgery for patients with a reported history of metal sensitivity. In cases of metal hypersensitivity-related joint failure, surgical revision ultimately may be required. Knowledge about joint replacement hypersensitivity reactions becomes vital because the approach to the evaluation depends on appropriate testing to guide recommendations for future arthroplasty procedures. CONCLUSION: Evaluation of hypersensitivity reactions after total joint arthroplasty requires a systematic approach, including a careful history, targeted evaluation with skin testing, and in vitro studies. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.anai.2014.05.012 PMID: 24934108 [Indexed for MEDLINE]

Int Orthop. 2014 Nov;38(11):2231-6. doi: 10.1007/s00264-014-2367-1. Epub 2014 Jun 10. A prospective study concerning the relationship between metal allergy and post-operative pain following total hip and knee arthroplasty. Zeng Y(1), Feng W, Li J, Lu L, Ma C, Zeng J, Li F, Qi X, Fan Y. Author information: (1)Orthopadic Department of The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China, 13711456292@163.com. PURPOSE: A prospective study was conducted to detect whether a relationship exists between metal allergy and post-operative pain in total hip and knee arthroplasty patients. We postulated that to some extent a relationship does exist between them. MATERIALS AND METHODS: Patients who had undergone total hip and knee arthroplasty surgery because of hip and knee disease were included. The exclusion criteria were patients who were treated with immunosuppressor two weeks pre-operatively, skin conditions around the patch testing site, and other uncontrollable factors. Each patient agreed to patch testing for three days before surgery. Photographic images before patch testing, two and three days after patch testing were obtained to evaluate the final incidence of metal allergy. The patch tests contained 12 metal elements; chromium, cobalt, nickel, molybdenum, titanium, aluminium, vanadium, iron, manganese, tin, zirconium, and copper. Two independent observers evaluated the images. The results were divided into a non-metal allergy group and a metal allergy group. Pre-operative and postoperative VAS score, lymphocyte transforming test, and X-rays were collected to detect the relationship between metal allergy and post-operative pain following total hip and knee arthroplasty. RESULTS: There were 96 patients who underwent pre-operative patch testing. The overall metal allergy rate was 51.1% (49/96) in our study. Nickel, cobalt, manganese, and tin were the most common allergic metal elements in our study. Nine inappropriate cases were excluded, and 87 patients were finally included in our study. There were 36 metal allergy and 26 non-metal allergy patients in the THA group, while 11 metal allergy and 14 non-metal allergy patients were found in the TKA group. We found no relationship existed between metal allergy and post-surgery pain in total hip and knee arthroplasty. CONCLUSION: Pain caused by metal allergy usually presents as persistent and recurrent pain. The white cell count, C-reactive protein, erythrocyte sedimentation rate and postoperative radiographs were not affected. Currently, patch testing and lymphocyte transforming tests are used for metal allergy diagnosis. We deemed that a relationship between post-surgery pain and metal allergy in total hip and knee patients may exist to some extent. Larger samples and longer follow-up time are essential for further study. DOI: 10.1007/s00264-014-2367-1 PMID: 24910214 [Indexed for MEDLINE]

Int J Occup Med Environ Health. 2012 Sep;25(4):463-9. doi: 10.2478/S13382-012-0029-3. Epub 2012 Dec 3. Allergy to orthopedic metal implants - a prospective study. Kręcisz B(1), Kieć-Świerczyńska M, Chomiczewska-Skóra D. Author information: (1)Center of Occupational Allergy and Environmental Health, Nofer Institute of Occupational Medicine, Łódź, Poland. krecisz@imp.lodz.pl OBJECTIVES: Evaluation of the allergenic properties of the metal knee or hip joint implants 24 months post surgery and assessment of the relation between allergy to metals and metal implants failure. MATERIALS AND METHODS: The study was conducted in two stages. Stage I (pre-implantation) - 60 patients scheduled for arthroplasty surgery. Personal interview, dermatological examination and patch testing with 0.5% potassium dichromate, 1.0% cobalt chloride, 5.0% nickel sulfate, 2.0% copper sulfate, 2.0% palladium chloride, 100% aluminum, 1% vanadium chloride, 5% vanadium, 10% titanium oxide, 5% molybdenum and 1% ammonium molybdate tetrahydrate were performed. Stage II (post-surgery) - 48 subjects participated in the same procedures as those conducted in Stage I. RESULTS: Stage I - symptoms of "metal dermatitis" were found in 21.7% of the subjects: 27.9% of the females, 5.9% of the males. Positive patch test results were found in 21.7% of the participants, namely to: nickel (20.0%); palladium (13.3%); cobalt (10.0%); and chromium (5.9%). The allergy to metals was confirmed by patch testing in 84.6% of the subjects with a history of metal dermatitis. Stage II - 10.4% of the participants complained about implant intolerance, 4.2% of the examined persons reported skin lesions. Contact allergy to metals was found in 25.0% of the patients: nickel 20.8%, palladium 10.4%, cobalt 16.7%, chromium 8.3%, vanadium 2.1% Positive post-surgery patch tests results were observed in 10.4% of the patients. The statistical analysis of the pre- and post-surgery patch tests results showed that chromium and cobalt can be allergenic in implants. CONCLUSIONS: Metal orthopedic implants may be the primary cause of allergies. that may lead to implant failure. Patch tests screening should be obligatory prior to providing implants to patients reporting symptoms of metal dermatitis. People with confirmed allergies to metals should be provided with implants free from allergenic metals. DOI: 10.2478/S13382-012-0029-3 PMID: 23212287 [Indexed for MEDLINE]

J Bone Joint Surg Br. 2012 Nov;94(11 Suppl A):14-8. doi: 10.1302/0301-620X.94B11.30680. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. Lombardi AV Jr(1), Barrack RL, Berend KR, Cuckler JM, Jacobs JJ, Mont MA, Schmalzried TP. Author information: (1)The Ohio State University, Department of Orthopaedics and Department of Biomedical Engineering, 7277 Smith's Mill Road, Suite 200, New Albany, Ohio 43054, USA. lombardiav@joint-surgeons.com Since 1996 more than one million metal-on-metal articulations have been implanted worldwide. Adverse reactions to metal debris are escalating. Here we present an algorithmic approach to patient management. The general approach to all arthroplasty patients returning for follow-up begins with a detailed history, querying for pain, discomfort or compromise of function. Symptomatic patients should be evaluated for intra-articular and extra-articular causes of pain. In large head MoM arthroplasty, aseptic loosening may be the source of pain and is frequently difficult to diagnose. Sepsis should be ruled out as a source of pain. Plain radiographs are evaluated to rule out loosening and osteolysis, and assess component position. Laboratory evaluation commences with erythrocyte sedimentation rate and C-reactive protein, which may be elevated. Serum metal ions should be assessed by an approved facility. Aspiration, with manual cell count and culture/sensitivity should be performed, with cloudy to creamy fluid with predominance of monocytes often indicative of failure. Imaging should include ultrasound or metal artifact reduction sequence MRI, specifically evaluating for fluid collections and/or masses about the hip. If adverse reaction to metal debris is suspected then revision to metal or ceramic-on-polyethylene is indicated and can be successful. Delay may be associated with extensive soft-tissue damage and hence poor clinical outcome. DOI: 10.1302/0301-620X.94B11.30680 PMID: 23118373 [Indexed for MEDLINE]

J Bone Joint Surg Br. 2012 Aug;94(8):1126-34. doi: 10.1302/0301-620X.94B8.28135. Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review. Granchi D(1), Cenni E, Giunti A, Baldini N. Author information: (1)Rizzoli Orthopaedic Institute, Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Via di Barbiano 1/10, 40136 Bologna, Italy. donatella.granchi@ior.it We report a systematic review and meta-analysis of the peer-reviewed literature focusing on metal sensitivity testing in patients undergoing total joint replacement (TJR). Our purpose was to assess the risk of developing metal hypersensitivity post-operatively and its relationship with outcome and to investigate the advantages of performing hypersensitivity testing. We undertook a comprehensive search of the citations quoted in PubMed and EMBASE: 22 articles (comprising 3634 patients) met the inclusion criteria. The frequency of positive tests increased after TJR, especially in patients with implant failure or a metal-on-metal coupling. The probability of developing a metal allergy was higher post-operatively (odds ratio (OR) 1.52 (95% confidence interval (CI) 1.06 to 2.31)), and the risk was further increased when failed implants were compared with stable TJRs (OR 2.76 (95% CI 1.14 to 6.70)). Hypersensitivity testing was not able to discriminate between stable and failed TJRs, as its predictive value was not statistically proven. However, it is generally thought that hypersensitivity testing should be performed in patients with a history of metal allergy and in failed TJRs, especially with metal-on-metal implants and when the cause of the loosening is doubtful. DOI: 10.1302/0301-620X.94B8.28135 PMID: 22844057 [Indexed for MEDLINE]

Knee. 2012 Mar;19(2):144-7. doi: 10.1016/j.knee.2011.01.001. Epub 2011 Feb 2. Metal hypersensitivity in total knee arthroplasty: revision surgery using a ceramic femoral component - a case report. Bergschmidt P(1), Bader R, Mittelmeier W. Author information: (1)Department of Orthopaedics, University of Rostock, Germany. philipp.bergschmidt@med.uni-rostock.de We present a case involving the revision of a total knee arthroplasty with a metal femoral component using a ceramic implant due to metal hypersensitivity. A 58-year-old female patient underwent total knee arthroplasty (TKA) with a standard metal bicondylar knee system. She suffered from persistent pain and strong limitations in her range of motion (ROM) associated with flexion during the early postoperative period. Arthroscopic arthrolysis of the knee joint and intensive active and passive physical treatment, in combination with a cortisone regime, temporarily increased the ROM and reduced pain. No signs of low grade infection or other causes of implant failure were evident. Histology of synovial tissue revealed lymphoplasmacellular fibrinous tissue, consistent with a type IV allergic reaction. Allergometry (skin reaction) revealed type IV hypersensitivity against nickel-II-sulfate and palladium chloride. Revision surgery of the metal components was performed with a cemented ceramic femoral component (same bicondylar design) and a cemented titanium alloy tibial component. Postoperative evaluations were performed 10days, and 3 and 12months after the revision surgery. There was an increased ROM in flexion to 90° at the 12month follow-up. No swelling or effusion was observed at all clinical examinations after the revision surgery. No pain at rest and moderate walking pain were evident. The presented case demonstrates that ceramic implants are a promising solution for patients suffering from hypersensitivity to metal ions in total knee arthroplasty. Copyright © 2011 Elsevier B.V. All rights reserved. DOI: 10.1016/j.knee.2011.01.001 PMID: 21292491 [Indexed for MEDLINE]

Int J Occup Med Environ Health. 2006;19(3):178-80. Allergy to metals as a cause of orthopedic implant failure. Krecisz B(1), Kieć-Swierczyńska M, Bakowicz-Mitura K. Author information: (1)Department of Occupational Diseases, Nofer Institute of Occupational Medicine, Lódź, Poland. krecisz@imp.lodz.pl BACKGROUND: A constantly growing social demand for orthopedic implants has been observed in Poland. It is estimated that about 5% of patients experience post-operation complications. It is suspected that in this group of patients an allergic reaction contributes to rejection of metal implants. MATERIALS AND METHODS: The aim of our study was to assess contact allergy to metals in 14 people (9 women and 5 men) suffering from poor implant tolerance. In some of them, recurrent skin eruptions, generalized or nearby implants, have occurred and in 3 patients skin fistula was observed. These complaints appeared one year after operation. The patients underwent patch tests with allergens from the Chemotechnique Diagnostics (Malmö, Sweden), including nickel, chromium, cobalt, palladium, copper, aluminum. In addition, allergens, such as titanium, vanadium and molybdenum prepared by chemical laboratory in the Nofer Institute of Occupational Medicine, Lódiź, Poland, were introduced. RESULTS AND CONCLUSIONS: Of the 14 patients, 8 persons (5 women and 3 men) were sensitized to at least one metal, mostly to nickel (7/14) and chromium (6/14). Of the 8 sensitized patients, 3 were reoperated. Owing to the exchange of prosthesis the complaints subsided, including healing up skin fibulas. These facts weight in favor of the primeval sensitizing effect of metal prosthesis and the relation between allergy and clinical symptoms of poor tolerance to orthopedic implants. PMID: 17252668 [Indexed for MEDLINE]