International Orthopaedics

, Volume 43, Issue 10, pp 2323–2331 | Cite as

A case series of cementless revision total knee arthroplasty in patients with benzoyl peroxide allergy

  • Frank S. FröschenEmail author
  • Nadine Gravius
  • Jan-Frederic Lau
  • Thomas Martin Randau
  • Eva Kaup
  • Max J. Friedrich
  • Sascha Gravius
Original Paper



The contact allergens nickel, cobalt, and chromium are often discussed as possible triggers of allergic reactions to orthopedic implants. Additionally, acrylates and polymerization additives in bone cement (e.g., benzoyl peroxide (BPO)) have been implicated as triggers of eczema, wound healing disorders, and aseptic implant loosening. We report about six patients with aseptic loosening after total knee arthroplasty (TKA), who underwent revision surgery after testing positive for BPO hypersensitivity.


After clarification of possible other causes of implant failure, epicutaneous testing had been performed and the implants were replaced in a two-stage procedure with cementless, diaphyseal anchoring, hypoallergenic (TiNb-coated) revision endoprostheses.


Epicutaneous testing revealed a BPO allergy in all six patients and an additional nickel allergy in three of the six patients. There was no histopathological or microbiological evidence for a periprosthetic infection. The clinical follow-up showed a low level of pain with good function, a stable knee joint, and proper implant position. The Knee Society Score (KSS) with its subscales Knee Score and Functional Score improved post-operatively from 43 to 70 points and from 47.5 to 68.3 points, respectively. Two implant-specific complications occurred: femoral stress shielding two years post-operatively with no further need for action and aseptic loosening of the tibial stem with the need of revision three years post-operatively.


The regression of complaints after replacement with cementless and nickel-free revision implants suggests allergic implant intolerance. Implantation of a cementless, hypoallergenic endoprosthesis might, therefore, be a surgical treatment strategy in patients with evidence of allergies.


Allergy Benzoyl peroxide Nickel Metal Bone cement Total knee arthroplasty Revision 


Compliance with ethical standards

Conflict of interest

S. Gravius has received a speaker honorarium from Waldemar LINK GmbH and financial support from Waldemar LINK GmbH to participate at a surgery course. The other authors declare that they have no conflict of interest. No benefits have been or will be received from a commercial party related directly or indirectly to the subject matter of this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.


  1. 1.
    Thomas P, Thomsen M (2008) Allergiediagnostik bei Metallimplantatunverträglichkeit. Orthopade 37:131–135. CrossRefPubMedGoogle Scholar
  2. 2.
    Schuh A, Thomas P, Reinhold R, Holzwarth U, Zeiler G, Mahler V (2006) Allergie auf Knochenzementbestandteile nach Knieendoprothesenimplantation. Zentralblatt Für Chir 131:429–431. CrossRefGoogle Scholar
  3. 3.
    Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, Schneider J, Flaig M, Krenn V, Thomas B, Summer B (2015) Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern. Biomed Res Int 2015:1–9. CrossRefGoogle Scholar
  4. 4.
    Thomas P (2003) Allergien durch Implantatwerkstoffe. Orthopäde 32:60–64. CrossRefPubMedGoogle Scholar
  5. 5.
    Granchi D, Cenni E, Giunti A, Baldini N (2012) Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review. J Bone Joint Surg Br 94:1126–1134. CrossRefPubMedGoogle Scholar
  6. 6.
    Schäfer T, Böhler E, Ruhdorfer S, Weigl L, Wessner D, Filipiak B, Wichmann HE, Ring J (2001) Epidemiology of contact allergy in adults. Allergy 56:1192–1196CrossRefGoogle Scholar
  7. 7.
    Kaplan K, Della Valle CJ, Haines K, Zuckerman JD (2002) Preoperative identification of a bone-cement allergy in a patient undergoing total knee arthroplasty. J Arthroplast 17:788–791CrossRefGoogle Scholar
  8. 8.
    Dejobert Y, Piette F, Thomas P (2002) Contact dermatitis from benzoyl peroxide in dental prostheses. Contact Dermatitis 46:177–178CrossRefGoogle Scholar
  9. 9.
    Willert H-G, Buchhorn GH, Fayyazi A, Flury R, Windler M, Köster G, Lohmann CH (2005) Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints: a clinical and histomorphological study. JBJS 87:28–36CrossRefGoogle Scholar
  10. 10.
    Klimek L (2015) Allergiediagnostik in der Praxis: Was der Hausarzt wissen sollte. Dtsch Aerzteblatt Online.
  11. 11.
    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, Rüther W, Poremba C, Gehrke T (2013) Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses. Z Rheumatol 72:383–392. CrossRefPubMedGoogle Scholar
  12. 12.
    van Hove RP, Brohet RM, van Royen BJ, Nolte PA (2016) High correlation of the Oxford Knee Score with postoperative pain, but not with performance-based functioning. Knee Surg Sports Traumatol Arthrosc 24:3369–3375. CrossRefPubMedGoogle Scholar
  13. 13.
    Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG (2011) New definition for periprosthetic joint infection: from the workgroup of the musculoskeletal infection society. Clin Orthop 469:2992–2994. CrossRefPubMedGoogle Scholar
  14. 14.
    Wimmer MD, Randau TM, Petersdorf S, Pagenstert GI, Weißkopf M, Wirtz DC, Gravius S (2013) Evaluation of an interdisciplinary therapy algorithm in patients with prosthetic joint infections. Int Orthop 37:2271–2278. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bircher A, Friederich NF, Seelig W, Scherer K (2012) Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement. Contact Dermatitis 66:20–26. CrossRefPubMedGoogle Scholar
  16. 16.
    Hischebeth GTR, Randau TM, Molitor E, Wimmer MD, Hoerauf A, Bekeredjian-Ding I, Gravius S (2016) Comparison of bacterial growth in sonication fluid cultures with periprosthetic membranes and with cultures of biopsies for diagnosing periprosthetic joint infection. Diagn Microbiol Infect Dis 84:112–115. CrossRefPubMedGoogle Scholar
  17. 17.
    Morawietz L (2006) Proposal for a histopathological consensus classification of the periprosthetic interface membrane. J Clin Pathol 59:591–597. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Healy WL, Della Valle CJ, Iorio R, Berend KR, Cushner FD, Dalury DF, Lonner JH (2013) Complications of total knee arthroplasty: standardized list and definitions of the knee society. Clin Orthop Relat Res 471:215–220. CrossRefPubMedGoogle Scholar
  19. 19.
    Roberts TT, Haines CM, Uhl RL (2017) Allergic or hypersensitivity reactions to orthopaedic implants. J Am Acad Orthop Surg 25:693–702. CrossRefPubMedGoogle Scholar
  20. 20.
    Lohmann CH, Hameister R, Singh G (2017) Allergies in orthopaedic and trauma surgery. Orthop Traumatol Surg Res 103:75–81. CrossRefGoogle Scholar
  21. 21.
    Zeng Y, Feng W, Li J, Lu L, Ma C, Zeng J, Li F, Qi X, Fan Y (2014) A prospective study concerning the relationship between metal allergy and post-operative pain following total hip and knee arthroplasty. Int Orthop 38:2231–2236. CrossRefPubMedGoogle Scholar
  22. 22.
    Bozic KJ, Kamath AF, Ong K, Lau E, Kurtz S, Chan V, Vail TP, Rubash H, Berry DJ (2015) Comparative epidemiology of revision arthroplasty: failed THA poses greater clinical and economic burdens than failed TKA. Clin Orthop Relat Res 473:2131–2138. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Haddad FS, Cobb AG, Bentley G, Levell NJ, Dowd PM (1996) Hypersensitivity in aseptic loosening of total hip replacements. The role of constituents of bone cement. J Bone Joint Surg Br 78:546–549CrossRefGoogle Scholar
  24. 24.
    Kurtz SM, Ong KL, Lau E, Bozic KJ (2014) Impact of the economic downturn on total joint replacement demand in the United States: updated projections to 2021. J Bone Jt Surg-Am 96:624–630. CrossRefGoogle Scholar
  25. 25.
    Boeckler A, Morton D, Poser S, Dette K (2008) Release of dibenzoyl peroxide from polymethyl methacrylate denture base resins: an in vitro evaluation. Dent Mater 24:1602–1607. CrossRefPubMedGoogle Scholar
  26. 26.
    Dudda M, Godau P, Al-Benna S, Schildhauer TA, Gothner M (2013) Vitiligo and allergic complications from orthopaedic joint implants: the role of benzoyl peroxide. Recent Patents Inflamm Allergy Drug Discov 7:176–182CrossRefGoogle Scholar
  27. 27.
    Uter W, Rämsch C, Aberer W, Ayala F, Balato A, Beliauskiene A, Fortina AB, Bircher A, Brasch J, Chowdhury MM (2009) The European baseline series in 10 European countries, 2005/2006–results of the European Surveillance System on Contact Allergies (ESSCA). Contact Dermatitis 61:31–38CrossRefGoogle Scholar
  28. 28.
    Geier J, Lessmann H, Becker D, Thomas P (2008) Allergologische Diagnostik bei Verdacht auf Implantatunverträglichkeit: Hinweise für die Praxis: Eine Stellungnahme der Deutschen Kontaktallergie-Gruppe (DKG). Hautarzt 59:594–597. CrossRefPubMedGoogle Scholar
  29. 29.
    Eis D, Wolf U (2008) “Qualitätssicherung beim Lymphozytentransformationstest” – Addendum zum LTT-Papier der RKI-Kommission “Methoden und Qualitätssicherung in der Umweltmedizin”: Mitteilung der Kommission “Methoden und Qualitätssicherung in der Umweltmedizin”. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 51:1070–1076. CrossRefGoogle Scholar
  30. 30.
    Akil S, Newman JM, Shah NV, Ahmed N, Deshmukh AJ, Maheshwari AV (2018) Metal hypersensitivity in total hip and knee arthroplasty: current concepts. J Clin Orthop Trauma 9:3–6. CrossRefPubMedGoogle Scholar
  31. 31.
    Thomas P (2014) Clinical and diagnostic challenges of metal implant allergy using the example of orthopaedic surgical implants. Allergo J Int 23:179–185. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Guenther D, Thomas P, Kendoff D, Omar M, Gehrke T, Haasper C (2016) Allergic reactions in arthroplasty: myth or serious problem? Int Orthop 40:239–244. CrossRefPubMedGoogle Scholar
  33. 33.
    Witzleb W-C, Hanisch U, Kolar N, Krummenauer F, Guenther K-P (2007) Neo-capsule tissue reactions in metal-on-metal hip arthroplasty. Acta Orthop 78:211–220. CrossRefPubMedGoogle Scholar
  34. 34.
    Holzwarth U, Thomas P, Kachler W, Göske J, Schuh A (2005) Metallkundliche Differenzierung von Kobalt-Chrom-Legierungen für Implantate. Orthopade 34:1046–1051. CrossRefPubMedGoogle Scholar
  35. 35.
    Natu S, Sidaginamale RP, Gandhi J, Langton DJ, Nargol AVF (2012) Adverse reactions to metal debris: histopathological features of periprosthetic soft tissue reactions seen in association with failed metal on metal hip arthroplasties. J Clin Pathol 65:409–418. CrossRefPubMedGoogle Scholar
  36. 36.
    Lons A, Putman S, Pasquier G, Migaud H, Drumez E, Girard J (2017) Metallic ion release after knee prosthesis implantation: a prospective study. Int Orthop 41:2503–2508. CrossRefPubMedGoogle Scholar
  37. 37.
    Treudler R, Simon JC (2007) Benzoyl peroxide: is it a relevant bone cement allergen in patients with orthopaedic implants? Contact Dermatitis 57:177–180CrossRefGoogle Scholar
  38. 38.
    Fleischman AN, Azboy I, Fuery M, Restrepo C, Shao H, Parvizi J (2017) Effect of stem size and fixation method on mechanical failure after revision total knee arthroplasty. J Arthroplast. PubMedGoogle Scholar
  39. 39.
    Schwarzkopf R (2015) Total knee arthroplasty failure induced by metal hypersensitivity. Am J Case Rep 16:542–547. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Thakur RR, Ast MP, McGraw M, Bostrom MP, Rodriguez JA, Parks ML (2013) Severe persistent synovitis after cobalt-chromium total knee arthroplasty requiring revision. Orthopedics 36:e520–e524. CrossRefPubMedGoogle Scholar
  41. 41.
    Hackenberg RK, Nessler J, König DP (2018) First application of segmental trabecular metal cones in a custom-made revision tumor prosthesis of the knee: a technical note. Technol Health Care 26:195–202. CrossRefPubMedGoogle Scholar

Copyright information

© SICOT aisbl 2018

Authors and Affiliations

  • Frank S. Fröschen
    • 1
    Email author
  • Nadine Gravius
    • 1
  • Jan-Frederic Lau
    • 2
  • Thomas Martin Randau
    • 1
  • Eva Kaup
    • 1
  • Max J. Friedrich
    • 1
  • Sascha Gravius
    • 1
  1. 1.Department of Orthopaedics and Trauma SurgeryUniversity Hospital BonnBonnGermany
  2. 2.Department of PathologyUniversity Hospital BonnBonnGermany

Personalised recommendations