Metal Allergy pp 321-330 | Cite as

Diagnostic Work-Up of Patients with Metal Implant Failure

  • Peter ThomasEmail author
  • Burkhard Summer


In patients with metal implant failure, all clinical and etiological factors need to be considered, and common causes like infection, malpositioning, or mechanical elicitors should be ruled out. Implant allergy often is a diagnosis of exclusion, supported by evaluation with allergy diagnostics. In view of the lack of consensus, this chapter reports on the different diagnostic approaches suggested by expert groups. Ideally, there should be combined evaluation including patch testing (PT), histology, and lymphocyte transformation testing (LTT). There are several suggestions/limitations. PT: pre-implant testing should be only done in patients with self-reported history of “adverse reaction” to metals—but not as a general prophetic “biocompatibility” test. While an additional late reading (day 6 or 7) increases the yield of positive test reactions, there exist no evaluated test preparations for many implant metals. Testing with metal discs is not recommended. Histology: peri-implant lymphocytic infiltration is suggestive of, but not definitive for, implant allergy. LTT: this rather scientific assay demonstrates sensitization and needs to be evaluated and interpreted with care. Accordingly, each patient should be individually evaluated.


  1. 1.
    Wengler A, Nimptsch U, Mansky T. Hip and knee replacement in Germany and the USA–analysis of individual inpatient data from German and US hospitals for the years 2005 to 2011. Ärzteblatt Int. 2014;111(23–24):9.Google Scholar
  2. 2.
    Liow MH, Kwon YM. Metal-on-metal total hip arthroplasty: risk factors for pseudotumours and clinical systematic evaluation. Int Orthop. 2016;41:885–92.CrossRefGoogle Scholar
  3. 3.
    Kalson NS, Borthwick LA, Mann DA, Deehan DJ, Lewis P, Mann C, Mont MA, Morgan-Jones R, Oussedik S, Williams FM, Toms A, Argenson JN, Bellemans J, Bhave A, Furnes O, Gollwitzer H, Haddad FS, Hofmann S, Krenn V. International consensus on the definition and classification of fibrosis of the knee joint. The bone & joint journal. 2016;98-B(11):1479–88.CrossRefGoogle Scholar
  4. 4.
    Thomas P, Ständer S, Stauner K, Schraml A, Banke IJ, Gollwitzer H, Burgkart R, Prodinger PM, Schneider S, Pritschet M, Mazoochian F, Schopf C, Summer B. Arthroplasty patients and nickel sensitization: what do patch test and lymphocyte transformation test tell us. Sem Arthroplasty. 2013;24(4):261–4.CrossRefGoogle Scholar
  5. 5.
    Thomas P, Summer B. Diagnosis and management of patients with allergy to metal implants. Expert Rev Clin Immunol. 2015;11(4):501–9.CrossRefGoogle Scholar
  6. 6.
    Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, Schneider J, Flaig M, Krenn V, Thomas B, Summer B. Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern. Biomed Res Int. 2015;2015:910156.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Schalock PC, Menne T, Johansen JD, Taylor JS, Maibach HI, Liden C, Bruze M, Thyssen JP. Hypersensitivity reactions to metallic implants–diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis. 2012;66(1):4–19.CrossRefGoogle Scholar
  8. 8.
    Thyssen JP, Menne T, Schalock PC, Taylor JS, Maibach HI. Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic orthopaedic implants before and after surgery. Br J Dermatol. 2011;164(3):473–8.PubMedGoogle Scholar
  9. 9.
    Teo Wendy ZW, Schalock PC. Hypersensitivity reactions to implanted metal devices: facts and fictions. J Investig Allergol Clin Immunol. 2016;26(5):279–94.CrossRefGoogle Scholar
  10. 10.
    Schalock PC, Crawford G, Nedorost S, Scheinman PL, Atwater AR, Mowad C, Brod B, Ehrlich A, Watsky KL, Sasseville D, Silvestri D, Worobec SM, Elliott JF, Honari G, Powell DL, Taylor J, DeKoven J. Patch testing for evaluation of hypersensitivity to implanted metal devices: a perspective from the American contact dermatitis society. Dermatitis. 2016;27(5):241–7.CrossRefGoogle Scholar
  11. 11.
    Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis. 2011;22(2):65–79.PubMedGoogle Scholar
  12. 12.
    Amini M, Mayes WH, Tzeng A, Tzeng TH, Saleh KJ, Mihalko WM. Evaluation and management of metal hypersensitivity in total joint arthroplasty: a systematic review. J Long-Term Eff Med Implants. 2014;24(1):25–36.CrossRefGoogle Scholar
  13. 13.
    Mitchelson AJ, Wilson CJ, Mihalko WM, Grupp TM, Manning BT, Dennis DA, Goodman SB, Tzeng TH, Vasdev S, Saleh KJ. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty. Biomed Res Int. 2015;2015:137287.CrossRefGoogle Scholar
  14. 14.
    Thomas P, Summer B, Sander CA, Przybilla B, Thomas M, Naumann T. Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T-cell infiltrate and TH1-type cytokine expression in the peri-implantar tissue. Allergy. 2000;55(10):969–72.CrossRefGoogle Scholar
  15. 15.
    Hallab NJ, Caicedo M, Finnegan A, Jacobs JJ. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty. J Orthop Surg Res. 2008;3:6.CrossRefGoogle Scholar
  16. 16.
    Granchi D, Cenni E, Giunti A, Baldini N. Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review. J Bone Joint Surg. 2012;94(8):1126–34.CrossRefGoogle Scholar
  17. 17.
    Munch HJ, Jacobsen SS, Olesen JT, Menne T, Soballe K, Johansen JD, Thyssen JP. The association between metal allergy, total knee arthroplasty, and revision: study based on the Danish Knee Arthroplasty Register. Acta Orthop. 2015;86(3):378–83.CrossRefGoogle Scholar
  18. 18.
    Thienpont E, Berger Y. No allergic reaction after TKA in a chrome-cobalt-nickel-sensitive patient: case report and review of the literature. Knee Surg Sports traumato Arthros. 2013;21(3):636–40.CrossRefGoogle Scholar
  19. 19.
    Carlsson A, Moller H. Implantation of orthopaedic devices in patients with metal allergy. Acta Derm Venereol. 1989;69(1):62–6.PubMedGoogle Scholar
  20. 20.
    Thomas P, Stauner K, Schraml A, Mahler V, Banke IJ, Gollwitzer H, Burgkart R, Prodinger PM, Schneider S, Pritschet M, Mazoochian F, Schopf C, Steinmann A, Summer B. Characteristics of 200 patients with suspected implant allergy compared to 100 symptom-free arthroplasty patients. Orthopade. 2013;42(8):607–13. Epub 2013/08/03. Charakteristika von 200 Patienten mit Verdacht auf Implantatallergie im Vergleich zu 100 beschwerdefreien EndoprothesentragernCrossRefGoogle Scholar
  21. 21.
    Thomas P, Schuh A, Ring J, Thomsen M. Orthopedic surgical implants and allergies: joint statement by the implant allergy working group (AK 20) of the DGOOC (German association of orthopedics and orthopedic surgery), DKG (German contact dermatitis research group) and dgaki (German society for allergology and clinical immunology). Orthopade. 2008;37(1):75–88.CrossRefGoogle Scholar
  22. 22.
    Geier J, Lessmann H, Becker D, Thomas P. Allergy diagnostics in suspected implant intolerance: practical approach. A position paper of the German Contact Dermatitis Research Group (DKG). Hautarzt. 2008;59(7):594–7.CrossRefGoogle Scholar
  23. 23.
    Josefson A, Farm G, Meding B. Validity of self-reported nickel allergy. Contact Dermatitis. 2010;62(5):289–93.CrossRefGoogle Scholar
  24. 24.
    Schnuch A, Aberer W, Agathos M, Becker D, Brasch J, Elsner P, Frosch PJ, Fuchs T, Geier J, Hillen U, Loffler H, Mahler V, Richter G, Szliska C. Performing patch testing with contact allergens. J Dtsch Dermatol Ges. 2008;6(9):770–5.PubMedGoogle Scholar
  25. 25.
    Thomas P, Geier J, Dickel H, Diepgen T, Hillen U, Kreft B, Schnuch A, Szliska C, Mahler V. DKG statement on the use of metal alloy discs for patch testing in suspected intolerance to metal implants. J Dtsch Dermatol Ges. 2015;13(10):1001–4.PubMedGoogle Scholar
  26. 26.
    Thomas P, Geier J, Dickel H, Diepgen T, Hillen U, Kreft B, Schnuch A, Szliska C, Mahler V. Should metal alloy discs be used for patch testing in suspected metal implant intolerance reaction? Orthopade. 2015;44(11):905–8.CrossRefGoogle Scholar
  27. 27.
    Geier J, Gefeller O, Wiechmann K, Fuchs T. Patch test reactions at D4, D5 and D6. Contact Dermatitis. 1999;40(3):119–26.CrossRefGoogle Scholar
  28. 28.
    Madsen JT, Andersen KE. Outcome of a second patch test reading of TRUE Tests(R) on D6/7. Contact Dermatitis. 2013;68(2):94–7.CrossRefGoogle Scholar
  29. 29.
    Ahlgren C, Isaksson M, Moller H, Axell T, Liedholm R, Bruze M. The necessity of a test reading after 1 week to detect late positive patch test reactions in patients with oral lichen lesions. Clin Oral Investig. 2014;18(5):1525–31.CrossRefGoogle Scholar
  30. 30.
    Thomas B, Kulichova D, Wolf R, Summer B, Mahler V, Thomas P. High frequency of contact allergy to implant and bone cement components, in particular gentamicin, in cemented arthroplasty with complications: usefulness of late patch test reading. Contact Dermatitis. 2015;73(6):343–9.CrossRefGoogle Scholar
  31. 31.
    Simpson PM, Dall GF, Breusch SJ, Heisel C. In vitro elution and mechanical properties of antibiotic-loaded SmartSet HV and Palacos R acrylic bone cements. Orthopade. 2005;34(12):1255–62.CrossRefGoogle Scholar
  32. 32.
    Wahlig H, Dingeldein E. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand. 1980;51(1):49–56.CrossRefGoogle Scholar
  33. 33.
    Svedman C, Ekqvist S, Moller H, Bjork J, Pripp CM, Gruvberger B, Holmstrom E, Gustavsson CG, Bruze M. A correlation found between contact allergy to stent material and restenosis of the coronary arteries. Contact Dermatitis. 2009;60(3):158–64.CrossRefGoogle Scholar
  34. 34.
    Kreft B, Thomas P, Steinhauser E, Vass A, Summer B, Wohlrab J. Erythema and swelling after im-plantation of a cardioverter defibrillator (ICD). Dtsch Med Wochenschr. 2015;140(19):1462–4.CrossRefGoogle Scholar
  35. 35.
    Kubba R, Taylor JS, Marks KE. Cutaneous complications of orthopedic implants. A two-year prospective study. Arch Dermatol. 1981;117(9):554–60.CrossRefGoogle Scholar
  36. 36.
    Aneja S, Taylor JS, Billings SD, Honari G, Sood A. Post-implantation erythema in 3 patients and a review of reticular telangiectatic erythema. Contact Dermatitis. 2011;64(5):280–8.CrossRefGoogle Scholar
  37. 37.
    Kulichova D, Gehrke T, Kendoff D, Summer B, Parvizi J, Thomas P. Metal hypersensitivity mimicking Periprosthetic erysipelas-like infection. JBJS Case Connect. 2014;4(3):e65.CrossRefGoogle Scholar
  38. 38.
    Mensing CH, Krengel S, Tronnier M, Wolff HH. Reactive angioendotheliomatosis: is it 'intravascular histiocytosis'? JEADV. 2005;19(2):216–9.PubMedGoogle Scholar
  39. 39.
    Krenn V, Thomas P, Thomsen M, Kretzer JP, Usbeck S, Scheuber L, Perino G, Ruther W, v Welser R, Hopf F, Huber M. Histopathological particle algorithm: particle identification in the synovia and the SLIM. Z Rheumatol. 2014;73(7):639–49.CrossRefGoogle Scholar
  40. 40.
    Morawietz L, Classen RA, Schroder JH, Dynybil C, Perka C, Skwara A, Neidel J, Gehrke T, Frommelt L, Hansen T, Otto M, Barden B, Aigner T, Stiehl P, Schubert T, Meyer-Scholten C, Konig A, Strobel P, Rader CP, Kirschner S, Lintner F, Ruther W, Bos I, Hendrich C, Kriegsmann J, Krenn V. Proposal for a histopathological consensus classification of the periprosthetic interface membrane. J Clin Pathol. 2006;59(6):591–7.CrossRefGoogle Scholar
  41. 41.
    Krenn V, Morawietz L, Kienapfel H, Ascherl R, Matziolis G, Hassenpflug J, Thomsen M, Thomas P, Huber M, Schuh C, Kendoff D, Baumhoer D, Krukemeyer MG, Perino G, Zustin J, Berger I, Ruther W, Poremba C, Gehrke T. Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses. Z Rheumatol. 2013;72(4):383–92.CrossRefGoogle Scholar
  42. 42.
    Krenn V, Morawietz L, Jakobs M, Kienapfel H, Ascherl R, Bause L, Kuhn H, Matziolis G, Skutek M, Gehrke T. Joint endoprosthesis pathology. Histopathological diagnostics and classification. Pathologe. 2011;32(3):210–9.CrossRefGoogle Scholar
  43. 43.
    Morawietz L, Tiddens O, Mueller M, Tohtz S, Gansukh T, Schroeder JH, Perka C, Krenn V. Twenty-three neutrophil granulocytes in 10 high-power fields is the best histopathological threshold to differentiate between aseptic and septic endoprosthesis loosening. Histopathology. 2009;54(7):847–53.CrossRefGoogle Scholar
  44. 44.
    Parvizi J, Gehrke T, editors. In: Proceedings of the international consensus meeting on periprosthetic joint infection. International consensus meeting on periprosthetic joint infection. Data Trace Publishing Company; 2013.Google Scholar
  45. 45.
    Zmistowski B, Della Valle C, Bauer TW, Malizos KN, Alavi A, Bedair H, Booth RE, Choong P, Deirmengian C, Ehrlich GD, Gambir A, Huang R, Kissin Y, Kobayashi H, Kobayashi N, Krenn V, Lorenzo D, Marston SB, Meermans G, Perez J, Ploegmakers JJ, Rosenberg A, Simpfendorfer C, Thomas P, Tohtz S, Villafuerte JA, Wahl P, Wagenaar FC, Witzo E. Diagnosis of periprosthetic joint infection. J Orthop Res. 2014;32(Suppl 1):S98–107.PubMedGoogle Scholar
  46. 46.
    Willert HG, Buchhorn GH, Fayyazi A, Flury R, Windler M, Koster G, Lohmann CH. Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study. J Bone Joint SurgAm. 2005;87(1):28–36.CrossRefGoogle Scholar
  47. 47.
    Davies AP, Willert HG, Campbell PA, Learmonth ID, Case CP. An unusual lymphocytic perivascular infiltration in tissues around contemporary metal-on-metal joint replacements. J Bone Joint Surg Am. 2005;87(1):18–27.CrossRefGoogle Scholar
  48. 48.
    Goodman SB, Gibon E, Yao Z. The basic science of periprosthetic osteolysis. Instr Course Lect. 2013;62:201–6.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Gallo J, Vaculova J, Goodman SB, Konttinen YT, Thyssen JP. Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement. Acta Biomater. 2014;10(6):2354–66.CrossRefGoogle Scholar
  50. 50.
    Thomas P, von de Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, Schneider J, Flaig M, Krenn V, Thomas B, Summer B. Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern. Biomed Red Int. 2015;2015:910156.Google Scholar
  51. 51.
    Summer B, Paul C, Mazoochian F, Rau C, Thomsen M, Banke I, Gollwitzer H, Dietrich KA, Mayer-Wagner S, Ruzicka T, Thomas P. Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni. Contact Dermatitis. 2010;63(1):15–22.CrossRefGoogle Scholar
  52. 52.
    Hallab NJ, Anderson S, Stafford T, Glant T, Jacobs JJ. Lymphocyte responses in patients with total hip arthroplasty. JOrthopRes. 2005;23(2):384–91.CrossRefGoogle Scholar
  53. 53.
    Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59(8):809–20.CrossRefGoogle Scholar
  54. 54.
    Ständer S, Oppel E, Thomas P, Summer B. Evaluation of lymphocyte transformation test as compared to patch test in nickel allergy diagnosis. Contact Dermatitis. 2016;76:228–34.CrossRefGoogle Scholar
  55. 55.
    Summer B, Stander S, Kapp F, Thomas P. Role of the lymphocyte transformation test in the evaluation of metal sensitization. Hautarzt. 2016;67(5):380–4.CrossRefGoogle Scholar
  56. 56.
    Pacheco K, Barker L, Maier L, Erb S, Sills M, Knight V. Development of a validated blood test for nickel sensitization. J Allergy Clin Immunol. 2013;132(3):767–9. Epub 2013/05/16CrossRefGoogle Scholar
  57. 57.
    “Quality assurance in the lymphocyte transformation test”–addendum to the LTT publication “Methods and quality assurance in environmental medicine” by the RKI Committee. “Methods and quality assurance in environmental medicine” report by the committee. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2008;51(9):1070–6.Google Scholar
  58. 58.
    Canadian Agency for Drugs and Technologies in Health (CADTH). Lymphocyte Transformation Testing (LTT) or Lymphocyte Proliferation Testing (LPT) for Hip or Knee Arthroplasty: A Review of Clinical and Cost–Effectiveness, and Evidence–Based Guidelines. In: CADTH Rapid responses service; 2012.Google Scholar
  59. 59.
    Thomas P, Braathen LR, Dorig M, Aubock J, Nestle F, Werfel T, Willert HG. Increased metal allergy in patients with failed metal-on-metal hip arthroplasty and peri-implant T-lymphocytic inflammation. Allergy. 2009;64(8):1157–65.CrossRefGoogle Scholar
  60. 60.
    Beecker J, Gordon J, Pratt M. An interesting case of joint prosthesis allergy. Dermatitis. 2009;20(2):E4–9.PubMedGoogle Scholar
  61. 61.
    Svedman C, Moller H, Gruvberger B, Gustavsson CG, Dahlin J, Persson L, Bruze M. Implants and contact allergy: are sensitizing metals released as haptens from coronary stents? Contact Dermatitis. 2014;71(2):92–7.CrossRefGoogle Scholar
  62. 62.
    Thomas P, Thomas M, Summer B, Dietrich K, Zauzig M, Steinhauser E, Krenn V, Arnholdt H, Flaig MJ. 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. 2011;93(11):e61.CrossRefGoogle Scholar
  63. 63.
    Schalock PC, Thyssen JP. Metal hypersensitivity reactions to implants: opinions and practices of patch testing dermatologists. Dermatitis. 2013;24(6):313–20.CrossRefGoogle Scholar
  64. 64.
    Hallock K, Vaughn NH, Juliano P, Marks JG. Metal hypersensitivity and orthopedic implants: a survey of orthopedic surgeons. Dermatitis. 2016;28:76–80.CrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Klinik und Poliklinik für Dermatologie und AllergologieLudwig-Maximilians-Universität MünchenMunichGermany

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