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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2016

Open Access 01-12-2016 | Research article

Hypersensitivity reactions to metal implants: laboratory options

Authors: Anna Maria Carossino, Christian Carulli, Simone Ciuffi, Roberto Carossino, Giorgia Donata Zappoli Thyrion, Roberto Zonefrati, Massimo Innocenti, Maria Luisa Brandi

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

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Abstract

Background

All implant compounds undergo an electrochemical process when in contact with biological fluids, as well as mechanical corrosion due to abrasive wear, with production of metal debris that may inhibit repair processes. None of the commonly-used methods can diagnose implant allergies when used singly, therefore a panel of tests should be performed on allergic patients as pre-operative screening, or when a postoperative metal sensitisation is suspected.

Methods

We analysed patients with painful prostheses and subjects prone to allergies using the Patch Test in comparison with the Lymphocyte Transformation Test. Cytokine production was evaluated to identify prognostic markers for early diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal rearrangement was visualised by confocal microscopy.

Results

Our results demonstrate that the Lymphocyte Transformation Test can identify patients who have a predisposition to develop allergic reactions and can confirm the diagnosis of hypersensitivity in patients with painful prostheses.
The prevalence of a Th2-cytokine pattern may be used to identify predisposition to the development of allergic diseases, while the selective presence of osteoclastogenic cytokines may be used as predictor of a negative outcome in patients with painful prosthesis.
The hypothesis of the prognostic value of these cytokines as early markers of aseptic loosening is attractive, but its confirmation would require extensive testing.

Conclusions

The Lymphocyte Transformation Test is the most suitable method for testing systemic allergies. We suggest that the combined use of the Patch Test and the Lymphocyte Transformation Test, associated with cytokine detection in selected patients, could provide a useful tool for preventive evaluation of immune reactivity in patients undergoing primary joint replacement surgery, and for clinical monitoring of the possible onset of a metal sensitization in patients with implanted devices.
Literature
1.
Ritter MA. The anatomical graduated component total knee replacement. A long-term evaluation with 20-years survival analysis. J Bone Joint Surg Br. 2009;91(6):745–9.CrossRefPubMed
2.
Carulli C, Matassi F, Nistri L, Civinini R, Innocenti M. Long-term survival of a flat-on-flat total condylar knee arthroplasty fixed with a hybrid cementing technique for tibial components. J Long Term Eff Med Implants. 2012;22(4):305–12.CrossRefPubMed
3.
Kurtz SM, Lau E, Ong K, Zhao K, Kelly M, Bozic KJ. Future young patient demand for primary and revision joint replacement: national projections from 2010 to 2030. Clin Orthop Relat Res. 2009;467(10):2606–12.CrossRefPubMedPubMedCentral
4.
Summer B, Paul C, Mazoochian F, Rau C, Thomsen M, Banke I, et al. 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.CrossRefPubMed
5.
Villano M, Carulli C, Puccini S, Soderi S, Innocenti M. Painful knee prosthesis: surgical approach. Clin Cases Miner Bone Metab. 2011;8(2):26–8.PubMedPubMedCentral
6.
Thomas P, Braathen LR, Dörig M, Auböck J, Nestle F, Werfel T, et al. Increased metal allergy in patients with failed metal-on-metal hip arthroplasty and periimplant T lymphocytic inflammation. Allergy. 2009;64(8):1157–65.CrossRefPubMed
7.
Hallab N, Merritt K, Jacobs JJ. Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg Am. 2001;83:428–36.CrossRefPubMed
8.
Jacobs JJ, Hallab NJ, Skipor AK, Urban RM. Metal degradation products: a cause for concern in metal-metal bearings? Clin Orthop Relat Res. 2003;417:139–47.
9.
Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis. 2011;22:65–79.PubMed
10.
Michel R, Nolte M, Reich M, Loer F. Systemic effect of implanted prostheses made of cobalt-chromium alloys. Arcgh Orthop Trauma Surg. 1991;110:61–74.CrossRef
11.
Urban RM, Jacobs JJ, Tomlinson MJ, Gavrilovic J, Black J, Peoc’h M. Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement. J Bone Joint Surg Am. 2000;82(4):457–76.CrossRefPubMed
12.
Hallab NJ, Caicedo M, Epstein R, McAllister K, Jacobs JJ. In vitro reactivity to implant metals demonstrates a person dependant association with both T-cell and B-cell activation. J Biomed Mat Res. 2010;92(2):667–82.
13.
Niki Y, Matsumoto H, Otani T, Yatabe T, Kondo M, Yoshimine F, et al. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials. 2005;26:1019–26.CrossRefPubMed
14.
Abu-Amer Y, Darwech I, Clohisy JC. Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies. Arthritis Res Ther. 2007;9(Suppl1):S6.CrossRefPubMedPubMedCentral
15.
Gawkrodger DJ. Metal sensitivities and orthopaedic implants revisited: the potential for metal allergy with the new metal-on-metal joint prostheses. Br J Dermatol. 2003;148(6):1089–93.CrossRefPubMed
16.
Looney RJ, Schwarz EM, Boyd A, O’Keefe RJ. Periprosthetic osteolysis: an immunologist’s update. Curr Opin Rheumatol. 2006;18(1):80–7.CrossRefPubMed
17.
Belsito DV. The diagnostic evaluation, treatment, and prevention of allergic contact dermatitis in the new millennium. J Allergy Clin Immunol. 2000;105:409–20.CrossRefPubMed
18.
19.
Hallab NJ. Lymphocyte transformation testing for quantifying metal implant related hypersensitivity responses. Dermatitis. 2004;15:82–90.CrossRefPubMed
20.
Thyssen JP, Menné T, Schalock PC, Taylor JS, Maibach HI. Pragmatic approach to the clinical workup of patients with putative allergic disease to metallic orthopaedic implants before and after surgery. Br J Dermatol. 2011;164(3):473–8.PubMed
21.
Innocenti M, Civinini R, Carulli C, Matassi F, Villano M. The 5-year results of an oxidized zirconium femoral component for TKA. Clin Orthop Relat Res. 2010;46(5):1258–63.CrossRef
22.
Iida T, Minoda Y, Kadoya Y, Matsui Y, Kobayashi A, Iwaki H, et al. Mid-term clinical results of alumina medial pivot total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2012;20(8):1514–9.CrossRefPubMed
23.
Wilkinson DS, Fregert S, Magnusson B, Bandmann HJ, Calnan CD, Cronin E, et al. Terminology of contact dermatitis. Acta Derm Venereol. 1970;50:287–92.PubMed
24.
Bourke J, Coulson I, English J. British association of dermatologists. Guidelines for care of contact dermatitis. Br J Dermatol. 2001;145:877–85.CrossRefPubMed
25.
Bourke J, Coulson I, English J. British Association of Dermatologists Therapy Guidelines and audit subcommittee. Guidelines for the management of contact dermatitis: an update. Br J Dermatol. 2009;160(5):946–54.CrossRefPubMed
26.
Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, et al. 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.PubMedPubMedCentral
27.
Altman DG. Practical statistics for medical research. 1st ed. London: Chapman & Hall; 1991.
28.
Piscitelli P, Iolascon G, Innocenti M, Civinini R, Rubinacci A, Muratore M, et al. Painful prosthesis: approaching the patient with persistent pain following total hip and knee arthroplasty. Clin Cases Miner Bone Metab. 2013;10(2):97–110.PubMedPubMedCentral
29.
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618–25.CrossRefPubMed
30.
31.
32.
Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities, and post-operative determinants. Pain. 2011;152:566–72.CrossRefPubMed
33.
Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF. Allergic and irritant contact dermatitis. Eur J Dermatol. 2009;19(4):325–32.PubMed
34.
Brasch J, Henseler T, Aberer W, Bäuerle G, Frosch PJ, Fuchs T, et al. Reproducibility of patch tests. A multicenter study of synchronous left versus right sided patch tests by the German contact dermatitis research group. J Am Acad Dermatol. 1994;3:584–91.CrossRef
35.
36.
Czarnobilska E, Jenner B, Kaszuba-Zwoinska J, Kapusta M, Obtułowicz K, Thor P, et al. Contact allergy to nickel: patch test score correlates with IL5, but not with IFN gamma nickel specific secretion by peripheral blood lymphocytes. Ann Agric Environ Med. 2009;16(1):37–41.PubMed
37.
Buchwald D, Lundeberg L. Impaired responses of peripheral blood mononuclear cells to nickel in patients with nickel-allergic contact dermatitis and concomitant atopic dermatitis. Br J Dermatol. 2004;50(3):484–92.CrossRef
38.
Borg L, Christensen JM, Kristiansen J, Nielsen NH, Menné T, Poulsen LK. Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge. Arch Dermatol Res. 2000;292(6):285–91.CrossRefPubMed
39.
Jakobson E, Masjedi K, Ahlborg N, Lundeberg L, Karlberg AT, Scheynius A. Cytokine production in nickel-sensitized individuals analysed with enzyme-linked immunospot assay: possible implication for diagnosis. Br J Dermatol. 2002;147(3):442–9.CrossRefPubMed
40.
Falsafi-Amin H, Lundeberg L, Bakhiet M, Nordlind K. Early DNA synthesis and cytokine expression in the nickel activation of peripheral blood mononuclear cells in nickel-allergic subjects. Int Arch Allergy Immunol. 2000;123:170–6.CrossRefPubMed
41.
Inomoto M, Miyakawa S, Mishima H, Ochiai N. Elevated interleukin12 in pseudosynovial fluid in patients with aseptic loosening of hip prosthesis. J Orthop Sci. 2000;5:369–73.CrossRefPubMed
42.
Lee SK, Surh CD. Role of interleukin 7 in bone and T cell homeostasis. Immunol Rev. 2005;208:169–80.CrossRefPubMed
43.
Toraldo G, Roggia C, Qian WP, Pacifici R, Weitzmann MN. IL7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc Natl Acad Sci USA. 2003;100(1):125–30.CrossRefPubMed
44.
Hercus B, Saeed S, Revell PA. Expression profile of T cell associated molecules in the interfacial tissue of aseptically loosened prosthetic joints. J Mater Sci Mater Med. 2002;13(12):1153–6.CrossRefPubMed
45.
Thomas P, von der Helm C, Schopf C, Thomsen M, Frommelt L, Schneider J, et al. Peri-implant histology and cytokine pattern in metal-allergic knee arthroplasty patients with improvement after revision with hypoallergenic materials. Semin Arthroplast. 2012;23(4):268–72.CrossRef
46.
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.CrossRefPubMedPubMedCentral
47.
Ng VY, Lombardi Jr AV, Berend KR, Skeels MD, Adams JB. Perivascular lymphocytic infiltration is not limited to metal-on-metal bearings. Clin Orthop Relat Res. 2011;469(2):523–9.CrossRefPubMed
48.
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.PubMed
49.
Witzleb WC, Hanisch U, Kolar N, Krummenauer F, Guenther KP. Neo-capsule tissue reactions in metal-on-metal hip arthroplasty. Acta Orthop. 2007;78(2):211–20.CrossRefPubMed
50.
Clarke SA, Brooks RA, Hobby JL, Wimhurst JA, Myer BJ, Rushton N. Correlation of synovial fluid cytokine levels with histological and clinical parameters of primary and revision total hip and total knee replacements. Acta Orthop Scand. 2001;72(5):491–8.CrossRefPubMed
51.
Lassus J, Waris V, Xu JW, Li TF, Hao J, Nietosvaara Y, et al. Increased interleukin-8 (IL-8) expression is related to aseptic loosening of total hip replacement. Arch Orthop Trauma Surg. 2000;120(5–6):328–32.CrossRefPubMed
52.
Krenn V, Morawietz L, Kienapfel H, Ascherl R, Matziolis G, Hassenpflug J, et al. Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses. Z Rheumatol. 2013;72(4):383–92.CrossRefPubMed
Metadata
Title
Hypersensitivity reactions to metal implants: laboratory options
Authors
Anna Maria Carossino
Christian Carulli
Simone Ciuffi
Roberto Carossino
Giorgia Donata Zappoli Thyrion
Roberto Zonefrati
Massimo Innocenti
Maria Luisa Brandi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1342-y

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