In-vitro-Charakteristika der Nickel-Kontaktallergie unter Einbeziehen der periimplantären Immunreaktion bei Hüftimplantatträgern

In-vitro-Charakteristika der Nickel-Kontaktallergie wurden im Hinblick auf Proliferation, Zytokinexpression, Reifung dendritischer Zellen und Klonalität der proliferierenden Zellen hin untersucht. Die Erkenntnisse flossen im zweiten Teil in Gewebeuntersuchungen von periimplantärem Gewebe ein, das bei Revisionsoperation von Hüft-Endoprothesen gewonnen worden war. So wurden Hinweise auf allergie-assoziierte Implantatunverträglichkeitsreaktionen gesammelt und gewertet

Usefulness of lymphocyte transformation test and in vitro cytokine release in differentiating between independent and cross‐reacting nickel/palladium allergy

Background Often concomitant patch test (PT) reactivity to palladium (Pd) and nickel (Ni) is found. Objectives To determine whether lymphocyte transformation test (LTT) could be useful in discrimination between cross‐reacting or distinct PT results, and to compare the results with in vitro cytokine production upon Pd or Ni stimulation. Materials and Methods The study population consisted of two groups: 13 individuals with Pd PT reactions (10 with concomitant Ni PT reaction, 3 individuals with only Pd PT reactivity) and 10 Ni/Pd PT negative individuals. LTT and assessment of cytokine release (interferon‐gamma, interleukin‐5 [IL‐5], IL‐8, IL‐17A, tumor necrosis factor alpha) by cytometric bead assay were performed. Results All 10 patients with positive PT to Ni and Pd showed positive LTT to Ni (P < .05) as compared with the 10 Pd/Ni PT negative patients—but had no significant LTT reaction to Pd. In all, 9 out of 10 Pd/Ni PT negative patients were also LTT negative to Ni and 10 out of 10 to Pd. In the 3 only Pd PT reactors 2 out of 3 remained LTT negative to Ni and 0 out of 3 to Pd. As a major finding, cytokine production gave clearly enhanced IL‐5 response to Ni in Ni PT positive individuals (P < .05), whereas Pd PT reactivity was not linked with such enhanced IL‐5 production in vitro to Pd. Conclusions Pd and Ni sensitization are mostly found concomitantly, and cross‐reactivity is questioned. By different LTT reactions and particularly IL‐5 production in vitro, predominant Ni sensitization becomes more evident

Patients with Intolerance Reactions to Total Knee Replacement: Combined Assessment of Allergy Diagnostics, Periprosthetic Histology, and Peri-implant Cytokine Expression Pattern

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 inflammatory mediator analysis (IFN gamma, TNF alpha, IL1-beta, IL-2, IL-6, IL-8, IL-10, IL17, and TGF beta). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They 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 infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFN gamma expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies

Blood cytokine pattern and clinical outcome in knee arthroplasty patients: comparative analysis 5 years after standard versus "hypoallergenic" surface coated prosthesis implantation

Background and purpose - Metal sensitivity might provoke complications after arthroplasty. Correspondingly, coated "hypoallergenic" implants are of interest but long-term follow-up data are missing. Thus, we assessed immunological and clinical parameters in such patients. Patients and methods - 5 years' follow-up data were obtained from 3 centers, which used either a standard total knee replacement (TKR) or the identical implant with multilayer surface zirconium nitride based coating. Of the 196 patients (mean age 68 years (44-84), 110 females) 97 had arthroplasty with a coated surface, and 99 were treated by a standard TKR of the same type. Investigations were Knee Society Score (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), radiographic analysis, and cytokine measurement in peripheral blood. Pro- and anti-inflammatory cytokines were evaluated by cytometric beads assay and RT-PCR. Results - Survival rate (Kaplan-Meier) was 98% for coated and 97% for uncoated implants after 5 years. Mechanical axis and KSS pain score (42 vs. 41 (0-50)) were comparable. Most serum cytokine levels were comparable, but mean interleukin-8 and interleukin-10 levels were higher in the group with an uncoated implant. IL-8: 37 (SD 7.5) pg/mL vs. 1.1 (SD 4.3) (p < 0.001);IL-10: 3.6 (SD 2.5) vs. 0.3 (SD 1.8) pg/mL (p < 0.001). Interpretation - There was similar clinical outcome 5 years after standard and surface-coated TKR. In peripheral blood there was an increased pro-inflammatory status, i.e., significant elevation of IL-8 and the anti-inflammatory IL-10, after standard uncoated prosthesis. Any long-term effects of these cytokine changes are unknown

Allergy or Tolerance: Reduced Inflammatory Cytokine Response and Concomitant IL-10 Production of Lymphocytes and Monocytes in Symptom-Free Titanium Dental Implant Patients

Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the proinflammatory response and also potential tolerance favoring in vitro reactivity of human blood lymphocytes and monocytes (PBMC) to Ti in healthy individuals (14 without, 6 with complication-free dental Ti implants). The proliferation index (SI) in lymphocyte transformation test (LTT) and production of cytokines linked to innate immune response (IL-1β, IL-6, and TNFα) or immune regulation (IL-10) were assessed in response to TiO2 particles or Ti discs. In both groups, the Ti-LTT reactivity was not enhanced (e.g., SI<3). The control antigen tetanus toxoid (TT) gave adequate reactivity (median SI individuals without/with implant: 20.6±5.97/19.58±2.99). Individuals without implant showed higher cytokine response to Ti materials than individuals with symptom-free implants; for example, TiO2 rutile particle induced increase of IL-1β 70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6 individuals with complication-free Ti implants showed an ex vivo ongoing production of IL-10 (mean 4.18±2.98 pg/mL)-but none of the 14 controls showed such IL-10 production. Thus in vitro IL-1β-, IL-6-, and TNF-α production reflects “normal” unspecific immune response to Ti. This might be reduced by production of tolerogenic IL-10 in individuals with symptom-free Ti dental implants

Contact allergy to the Dexcom G6 glucose monitoring system-Role of 2,2 '-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate in the new adhesive

Background: Skin reactions to the glucose monitoring systems Dexcom G5 and G6 have been rare. In 2019, the components of the adhesive were exchanged for better skin fixation. Since then, more and more patients experienced severe skin reactions. A few months ago, 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) was identified as a new component in the adhesive of the G6 model. Furthermore, it was suspected that isobornyl acrylate (IBOA) was also a component of the exchanged adhesive. Objectives: Our objective was to investigate if MBPA plays a major role in the increasing skin problems of patients without a history of IBOA-sensitization. Furthermore, our aim was to examine whether IBOA is contained in the newer model adhesive and may also contribute to allergic contact dermatitis (ACD). Patients and Methods: Five patients with a newly occurred ACD caused by the glucose monitoring system Dexcom G6 were investigated. Patch testing including MBPA in three different concentrations, as well as IBOA, were performed. Gas chromatography-mass spectrometry of the newer system Dexcom G6 was carried out. Results: All patients were shown to be sensitized to MBPA, while MBPA 0,5% showed the strongest reaction. On the other hand, IBOA was tested negative. Conclusion: In our study group, MBPA was observed to be the triggering allergen of the recently changed adhesive

Increased inflammatory response is associated with less favorable functional results 5 years after total knee arthroplasty

Purpose Allergy against implant materials is discussed controversially and still not fully understood. Despite these controversies, a relevant number of patients receive hypoallergenic knee implants. The aim of this study was to compare a new coating system with the standard implant in total knee arthroplasty (TKA). Additionally, the influence of proinflammatory cytokines on patient-reported outcome measures (PROMs) was investigated. Methods 120 patients without known metal allergy and without previous metal implants were included. The patients were randomized to receive a coated or standard TKA of the same knee system. 105 patients completed the 5 year follow-up. Patient-reported outcome measures (PROMs) including knee function (Oxford Knee Score, OKS), quality of life (SF36) and UCLA activity scale were assessed. Additionally, several cytokines with a possible role in implant allergy were measured in patient`s serum (IL-1beta, IL-5, IL-6, IL-8, IL-10, IP-10, IFN γ, TNF α). Group comparison was performed using Mann–Whitney U test for continuous values and chi-square test for categorical values. Results There were no differences in PROMs between both groups at any follow-up. The majority of patients demonstrated no elevation of the measured blood cytokines. The blood cytokine pattern after 5 years demonstrated no differences between study groups. There was a significant association between elevated IL-8 values and worse results in the overall OKS (p = 0.041), the OKS function component (p = 0.004), the UCLA activity scale (p = 0.007) and the physical component of SF36 (p = 0.001). Conclusion There were no problems with the new coating during mid-term follow-up and no differences in PROMs between coated and standard TKA. Patients with an increased inflammatory response demonstrated worse functional results, regardless of the implant. Level of evidence I. Clinical trial registration The study protocol was registered in the US National Institutes of Health’s database (http:// www.clini caltr ials. gov) registry under NCT00862511