BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Department of Dermatology and Allergology University Hospital and University of Basel Basel Switzerland

Department of Dermatology and Allergology University Hospital Munich Germany

Department of Dermatology and Allergy National Allergy Research Centre University of Copenhagen Herlev and Gentofte Hospital Hellerup Denmark

Department of Dermatology and Allergy University of Copenhagen Herlev and Gentofte Hospital Hellerup Denmark

Department of Dermatology VU University Medical Center Amsterdam The Netherlands

Department of Dermatovenereology 3rd Faculty of Medicine Charles University and University Hospital of Kralovske Vinohrady Prague Czech Republic

Department of Occupational and Environmental Dermatology Lund University Skåne University Hospital Malmö Sweden

Department of Orthopaedic Surgery Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Orthopaedics Rostock University Medical Center Rostock Germany

Hospital MEDICAM Gryfice Poland

Institute of Clinical Medicine Copenhagen University Copenhagen Denmark

München Klinik gGmbH Munich Germany

MVZHZMD Trier GmbH Trier Germany

J Eur Acad Dermatol Venereol. 2025 Jan;39(1):231. doi: 10.1111/jdv.20466. PubMed

Zobrazit více v PubMed

Kubba R, Taylor JS, Marks KE. Cutaneous complications of orthopedic implants. A two‐year prospective study. Arch Dermatol. 1981;117(9):554–560.

Thomas RH, Rademaker M, Goddard NJ, Munro DD. Severe eczema of the hands due to an orthopaedic plate made of Vitallium. Br Med J. 1987;294(6564):106–107.

Hallab N, Merritt K, Jacobs JJ. Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg Am. 2001;83(3):428–436.

Kanerva L, Forstrom L. Allergic nickel and chromate hand dermatitis induced by orthopaedic metal implant. Contact Dermatitis. 2001;44(2):103–104.

Basko‐Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis. 2011;22(2):65–79.

Teo Wendy ZW, Schalock PC. Hypersensitivity reactions to implanted metal devices: facts and fictions. J Invest Allergol Clin Immunol. 2016;26(5):279–294.

Pacheco KA. Allergy to surgical implants. Clin Rev Allergy Immunol. 2019;56(1):72–85.

Munch HJ, Jacobsen SS, Olesen JT, Menne T, Soballe K, Johansen JD, et al. The association between metal allergy, total knee arthroplasty, and revision: study based on the Danish Knee Arthroplasty Register. Acta Orthop. 2015;86(3):378–383.

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):594–597.

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):473–478.

Schalock PC, Menne T, Johansen JD, Taylor JS, Maibach HI, Liden C, et al. Hypersensitivity reactions to metallic implants ‐ diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis. 2012;66(1):4–19.

Thomas P, Summer B. Diagnosis and management of patients with allergy to metal implants. Expert Rev Clin Immunol. 2015;11(4):501–509.

Thomas B, Summer B, Thyssen JP. Orthopedic implants. In: Johansen JD, Mahler V, Lepoittevin J‐P, Frosch P, editors. Contact dermatitis. 6th ed. Cham: Springer; 2021.

Ekqvist S, Svedman C, Lundh T, Moller H, Bjork J, Bruze M. A correlation found between gold concentration in blood and patch test reactions in patients with coronary stents. Contact Dermatitis. 2008;59(3):137–142.

Svedman C, Moller H, Gruvberger B, Gustavsson CG, Dahlin J, Persson L, et al. Implants and contact allergy: are sensitizing metals released as haptens from coronary stents? Contact Dermatitis. 2014;71(2):92–97.

Bjorkner B, Bruze M, Moller H, Salemark L. Allergic contact dermatitis as a complication of lid loading with gold implants. Dermatitis. 2008;19(3):148–153.

Poziomkowska‐Gesicka I, Summer B, Sokolowska M, Thomas P, Kurek M. Allergic contact dermatitis caused by hypersensitivity to gold ‐ description of a clinical case. Contact Dermatitis. 2018;78(5):363–365.

Contact dermatitis. 6th ed. Cham: Springer International Publishing; 2021.

Chen KJ, Thyssen JP, editors. From dermatitis to implant and device failure. Cham: Springer International Publishing; 2018.

Macfarlane AW, Curley RK, Graham RM, Lewis‐Jones MS, King CM. Delayed patch test reactions at days 7 and 9. Contact Dermatitis. 1989;20(2):127–132.

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):1525–1531.

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):343–349.

Research National Institute for Health Researche (NIfH). 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. University of York, Centre for Reviews and Dissemination: CADTH; 2012.

Yang S, Dipane M, Lu CH, Schmalzried TP, McPherson EJ. Lymphocyte transformation testing (LTT) in cases of pain following total knee arthroplasty: little relationship to histopathologic findings and revision outcomes. J Bone Joint Surg Am. 2019;101(3):257–264.

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):280–288.

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):2354–2366.

Krenn V, Morawietz L, Perino G, Kienapfel H, Ascherl R, Hassenpflug GJ, et al. Revised histopathological consensus classification of joint implant related pathology. Pathol Res Pract. 2014;210(12):779–786.

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.

Nair R, Aggarwal R, Khanna D. Methods of formal consensus in classification/diagnostic criteria and guideline development. Semin Arthritis Rheum. 2011;41(2):95–105.

Pua YH, Seah FJ, Poon CL, Tan JW, Alan Clark R, Liaw JS, et al. Age‐ and sex‐based recovery curves to track functional outcomes in older adults with total knee arthroplasty. Age Ageing. 2018;47(1):144–148.

Hartmann D, Letule V, Schneider JJ, Flaig MJ. Metal implant sensitivity: clinical and histological presentation. Hautarzt. 2016;67(5):373–379.

Johansen JD, Aalto‐Korte K, Agner T, Andersen KE, Bircher A, Bruze M, et al. European Society of Contact Dermatitis guideline for diagnostic patch testing ‐ recommendations on best practice. Contact Dermatitis. 2015;73(4):195–221.

Razak A, Ebinesan AD, Charalambous CP. Metal allergy screening prior to joint arthroplasty and its influence on implant choice: a delphi consensus study amongst orthopaedic arthroplasty surgeons. Knee Surg Relat Res. 2013;25(4):186–193.

Siljander BR, Chandi SK, Debbi EM, McLawhorn AS, Sculco PK, Chalmers BP. A comparison of clinical outcomes after total knee arthroplasty in patients with preoperative nickel allergy receiving cobalt chromium or nickel‐free implant. J Arthroplasty. 2023;38(7 Suppl 2):S194–S198.

Whiteside LA. Clinical results of revision TKA in patients with presumed metal and cement allergy. J Arthroplasty. 2022;37(6S):S250–S257.

Bruze M. Thoughts on implants and contact allergy. Arch Dermatol. 2008;144(8):1042–1044.

Fage SW, Muris J, Jakobsen SS, Thyssen JP. Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity. Contact Dermatitis. 2016;74(6):323–345.

Willert HG, Buchhorn GH, Fayyazi A, Flury R, Windler M, Koster G, et al. Metal‐on‐metal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study. J Bone Joint Surg Am. 2005;87(1):28–36.

Perino G, De Martino I, Zhang L, Xia Z, Gallo J, Natu S, et al. The contribution of the histopathological examination to the diagnosis of adverse local tissue reactions in arthroplasty. EFORT Open Rev. 2021;6(6):399–419.

Summer B, Stander S, Thomas P. Cytokine patterns in vitro, in particular IL‐5/IL‐8 ratio, to detect patients with nickel contact allergy. J Eur Acad Dermatol Venereol. 2018;32:1542–1548.

de Graaf NPJ, Bontkes HJ, Roffel S, Kleverlaan CJ, Rustemeyer T, Gibbs S, et al. Non‐heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel. Clin Exp Allergy. 2020;50(6):722–732.

De Graaf NPJ, Roffel S, Gibbs S, Kleverlaan CJ, Lopez Gonzalez M, Rustemeyer T, et al. Nickel allergy is associated with a broad spectrum cytokine response. Contact Dermatitis. 2023;88(1):10–17.

Muris J, Scheper RJ, Kleverlaan CJ, Rustemeyer T, van Hoogstraten IM, von Blomberg ME, et al. Palladium‐based dental alloys are associated with oral disease and palladium‐induced immune responses. Contact Dermatitis. 2014;71(2):82–91.

Spoerri I, Bircher AJ, Link S, Heijnen I, Scherer HK. Delayed‐type allergy to cobalt‐comparison of a flow cytometric lymphocyte proliferation test with patch testing. Contact Dermatitis. 2018;79(1):31–33.

Beecker J, Gordon J, Pratt M. An interesting case of joint prosthesis allergy. Dermatitis. 2009;20(2):E4–E9.

Dawson J, Fitzpatrick R, Murray D, Carr A. Questionnaire on the perceptions of patients about total knee replacement. J Bone Joint Surg Am. 1998;80(1):63–69.

Rabin R, de Charro F. EQ‐5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33(5):337–343.

Bircher A, Friederich NF, Seelig W, Scherer K. Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement. Contact Dermatitis. 2012;66(1):20–26.