Research Article Patients with Intolerance Reactions to Total Knee Replacement: Combined Assessment of Allergy Diagnostics, Periprosthetic Histology, and Peri-implant Cytokine Expression Pattern Peter Thomas, 1 Christine von der Helm, 1 Christoph Schopf, 2 Farhad Mazoochian, 2 Lars Frommelt, 3 Hans Gollwitzer, 4 Josef Schneider, 1 Michael Flaig, 1 Veit Krenn, 5 Benjamin Thomas, 1 and Burkhard Summer 1 1 Klinik und Poliklinik f¨ ur Dermatologie und Allergologie der Ludwig-Maximilians-Universit¨ at (LMU), Frauenlobstraße 9-11, 80337 M¨ unchen, Germany 2 Klinik und Poliklinik f¨ ur Orthop¨ adie der LMU, Marchioninistraße 15, 81377 M¨ unchen, Germany 3 Endoklinik, Abteilung f¨ ur Mikrobiologie, Holstenstraße 2, 22767 Hamburg, Germany 4 Klinik f¨ ur Orthop¨ adie und Sportorthop¨ adie der Technischen Universit¨ at M¨ unchen (TU), Ismaninger Straße 22, 81675 M¨ unchen, Germany 5 Institut f¨ ur Pathologie, Max-Planck-Straße 5, 54296 Trier, Germany Correspondence should be addressed to Peter Tomas; peter.thomas@med.uni-muenchen.de Received 4 July 2014; Accepted 8 September 2014 Academic Editor: Tomas M. Grupp Copyright © 2015 Peter Tomas et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic infammatory mediator analysis (IFN, TNF, IL1-, IL-2, IL-6, IL-8, IL- 10, IL17, and TGF). We analyzed 25 TKR patients with yet unexplained complications like pain, efusion, and reduced range of motion. Tey consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infltrates were seen and fbrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. Te latter also had marked periprosthetic IFN expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our fndings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies. 1. Introduction Hip and knee replacement are very successful surgical proce- dures to restore quality of life in osteoarthritis patients [1] and correspondingly implantation rates are steadily increasing [2]. However, in a substantial part of such patients implant failure leads to implant revision. A recent review lists a total knee replacement (TKR) revision rate of 9.5% in Germany and of 8.4% in the USA for the year 2011 [2]. Within the spectrum of conditions leading to TKR failure [3] adverse reactions may be found, but the role of allergy is still a controversial issue. Cutaneous metal allergy is frequent in the general population, for example, approximately 13% to nickel (Ni), 2% to cobalt (Co), and 1% to chromium (Cr) [4]. Either wear or corrosion leads to peri-implant and systemic metal (particularly Ni, Cr, or Co) exposure of arthroplasty patients [5], and correspondingly, prevalence of metal sensitivity in patients with failed implant is reported to be increased [6–8]. Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 910156, 9 pages http://dx.doi.org/10.1155/2015/910156