Contact Dermatitis

Hypersensitivity Reactions to Orthopedic Implants: What’s All the Hype?

Cutis. 2020 February;105(02):68-70

References

Dekoven JG, Warshaw EM, Zug KA, et al. North American Contact Dermatitis Group patch test results: 2015-2016. Dermatitis. 2018;29:297-309.
Gao X, He RX, Yan SG, et al. Dermatitis associated with chromium following total knee arthroplasty. J Arthroplasty. 2011;26:665.E613-665.E616.
Treudler R, Simon JC. Benzoyl peroxide: is it a relevant bone cement allergen in patients with orthopaedic implants? Contact Dermatitis. 2007;57:177-180.
Barranco VP, Soloman H. Eczematous dermatitis from nickel. JAMA. 1972;220:1244.
Engelhart S, Segal RJ. Allergic reaction to vanadium causes a diffuse eczematous eruption and titanium alloy orthopedic implant failure. Cutis. 2017;99:245-249.
Thyssen JP, Jakobsen SS, Engkilde K, et al. The association between metal allergy, total hip arthroplasty, and revision. Acta Orthop. 2009;80:646-652.
Münch HJ, Jacobsen SS, Olesen JT, et al. The association between metal allergy, total knee arthroplasty, and revision: study based on the Danish Knee Arthroplasty Register. Acta Orthop. 2015;86:378-383.
Jacobs JJ, Skipor AK, Patterson LM, et al. Metal release in patients who have had a primary total hip arthroplasty. a prospective, controlled, longitudinal study. J Bone Joint Surg Am. 1998;80:1447-1458.
Urban RM, Jacobs JJ, Tomlinson MJ, et al. 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;82:457-476.
Hallab N, Merritt K, Jacobs JJ. Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg Am. 2001;83:428-436.
Zondervan RL, Vaux JJ, Blackmer MJ, et al. Improved outcomes in patients with positive metal sensitivity following revision total knee arthroplasty. J Orthop Surg Res. 2019;14:182.
Atanaskova Mesinkovska N, Tellez A, Molina L, et al. The effect of patch testing on surgical practices and outcomes in orthopedic patients with metal implants. Arch Dermatol. 2012;148:687-693.
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Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis. 2011;22:65-79.
Schalock PC, Menné T, Johansen JD, et al. Hypersensitivity reactions to metallic implants—diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis. 2012;66:4-19.
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Schalock PC, Thyssen JP. Patch testers’ opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants. Dermatitis. 2013;24:183-185.

Clinical Presentation

Several clinical presentations of orthopedic IHRs have been described. Perhaps the most commonly recognized is a localized cutaneous eczematous eruption, with dermatitis typically overlying the site of the implanted material.^1,2,16 Generalized cutaneous eczematous IHRs also have been reported, including diffuse generalized dermatitis from a stainless steel orthopedic screw⁴ and nummular dermatitis attributed to vanadium in an orthopedic plate.⁵ Urticaria, vasculitis, and bullous cutaneous reactions, as well as extracutaneous complications, also have been reported.^14,15 Pain, edema, joint loosening or failure, and poor wound healing have been reported,¹² but it remains unclear whether these symptoms represent IHR.

Patch Testing for IHR

Several groups have published recommended patch test series for IHR.^12,14,15 Common components of implant patch testing panels include metals, adhesives (acrylates, epoxy resins) and antibiotics. Importantly, obtaining product information from the manufacturer of the suspected implant can guide which allergens to include in patch testing. Implant and metal panels also are available for commercial purchase.

Other Diagnostic Tests

We rarely (almost never) order LTTs in the workup for potential IHRs. This is an in vitro test that includes lymphocytes, metal ions, and the radioactive marker methyl-3H-thymidine. The goal of the test is to evaluate if patient lymphocytes are reactive or responsive to metal ions. A positive LTT suggests that lymphocytes can respond to the presence of metal ions but does not confirm allergy or the presence of IHR.

Typically, skin or tissue biopsies are not required to make a diagnosis of IHR; however, if performed, histopathology suggestive of IHR can support a suspected diagnosis. Typical findings include but are not limited to spongiotic dermatitis. Eosinophils may or may not be present. Metal disc testing has been utilized for orthopedic IHR but is not currently recommended due to low diagnostic yield. Prick testing rarely is used and also is not a primary method for diagnosis of IHR.¹⁷

Preimplantation Patch Testing

Expert opinion guidelines published by the American Contact Dermatitis Society (ACDS) state that routine preimplantation patch testing is not necessary; however, for those patients with a clear history of contact reactions to metal, preimplantation patch testing can be considered.¹⁷

Patch test results can influence the orthopedic surgeon’s choice of implant material. In one study, when preimplantation patch testing showed a positive patch test reaction to metals, the results influenced the surgeon’s decision-making in all cases.¹²

Postimplantation Patch Testing: Diagnostic Criteria for Metal IHR After Implantation

From 2012 to 2013, Schalock and Thyssen¹⁸ surveyed expert attendees at meetings of the European Society of Contact Dermatitis and the ACDS for their opinions on proposed diagnostic criteria for metal IHRs. Based on these results (N=119), the authors stratified 4 major and 5 minor diagnostic criteria, which were defined based on overall responses of meeting attendees. Major criteria included (1) chronic dermatitis beginning weeks to months after metallic implantation, (2) complete recovery after removal of the offending implant, (3) eruption overlying the metal implant, and (4) positive patch test reaction to a metal used in the implant. Minor criteria included (1) histology consistent with allergic contact dermatitis, (2) morphology consistent with dermatitis (ie, erythema, induration, papules, vesicles), (3) positive in vitro test to metals (eg, lymphocyte transformation test), (4) systemic allergic dermatitis reaction, and (5) therapy-resistant dermatitis reaction. The authors did not describe a scoring system for evaluation and confirmation of a diagnosis of IHR. Instead, the criteria should be used as general guidelines when evaluating patients for possible IHRs. From a standpoint of available diagnostic tests for metal IHR, 86.1% of experts agreed that a positive patch test reaction to a metal used in the implant was suggestive of a diagnosis, whereas a positive in vitro test to metals (LTT) was suggestive of a diagnosis for only 32.2% of respondents. This study was designed specifically for metal IHRs and therefore is not necessarily generalizable for nonmetal IHRs.¹⁸

Final Interpretation

We follow the 2016 ACDS guidelines¹⁷ and complete preimplantation patch testing only in the setting of suspected metal allergy and postimplantation patch testing based on the guidelines described by Schalock and Thyssen.¹⁸ However, an extended conversation is warranted prior to patch testing to ensure the patient fully understands the limitations of the test. Although we have both ordered the LTT, interpretation remains murky, and until this test is standardized, routine use is unlikely to benefit the patient. Until we are more reliably able to predict who will develop hypersensitivity to implanted metals, the decision to remove or revise an implant is one that should be made by a multidisciplinary team that includes the surgeon and the patient.