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An MRI Study. [1]. loosening of the implants (or implant failure). After skin patch testing, in-vitro lymphocyte proliferation testing is perhaps the most prevalent method of assessing hypersensitivities. Available at http://njhealth.multimedia-newsroom.com/index.php/2013/05/15/new-blood-test-finds-allergies-before-implant-surgery/. Hardware removal should be considered if there are any skin issues or signs of infection. Are children of working mothers more successful? [QxMD MEDLINE Link]. Correlation of allergy, metal levels, implant alloy, and implant damage in patients undergoing revision joint arthroplasties. [1]. Contact Dermatitis. zelik H, Vrana NE, Gudima A, Riabov V, Gratchev A, Haikel Y, et al. 2008 Dec. 23 (8):1212-8. Preoperative skin patch testing is not typically recommended unless there is a strong suggestion of established sensitivity by history, because of the slight chance of sensitization and the high-cost/low-yield results expected. [3] Carbohydrates/monosaccharides may have promising potential as materials with high immune compatibility and the ability to positively modify immune responses by stimulating dendritic cells to support T-cell phenotypes that are highly immunosuppressive. Top 10 Unproven Infertility Tests and Treatments, Immunotherapy With Radiotherapy Fails to Improve Prognosis of Patients With Stage IV Non-Small Cell Lung Cancer, Body Modifications: Dermatologic Reactions and Risks, New Biomaterial Vaccines Aim to Ward Off Future Pandemic Threats, UK Scientists Develop New Testing Method for Biomaterials. The presenting signs and symptoms of a nickel or other metal hypersensitivity to an implanted orthopedic device are variable but usually consist of the expected complaints of a patient with hardware failure. 2018 Jan-Mar. Newer implant designs have been developed specifically to minimize the release of metal ions. [QxMD MEDLINE Link]. 1984 Jan. 5 (1):47-53. 2019 Feb. 56 (1):72-85. Metal ion release may also be due to surgical technique in patients with metal-on-metal prostheses. First stainless steel implant in the left hip. Sicilia A, Cuesta S, Coma G, Arregui I, Guisasola C, Ruiz E, et al. If you log out, you will be required to enter your username and password the next time you visit. 1977 Mar. Tests that may be more specific include the lymphocyte transformation test (LTT) and the lymphokine MIF test (see below), which have been used to help diagnose metal hypersensitivity. Postoperatively, the patient did well, with evidence of fracture healing, full weightbearing, and full range of motion by 3 months after surgery. Acta Derm Venereol. Clin Mater. [40] This serves as a screening test for the possible presence of asymptomatic local soft-tissue reaction. Studies reveal that positive MIF test results to metals implanted in an orthopedic patient are well correlated with pain, swelling, and dermatologic reactions over that area. Infection, nonunion, aseptic loosening, other inflammatory conditions, mechanical failure of the implant, and malalignment issues must be excluded first before the problem is assumed to be an allergic reaction. 5th ed. This can cause numbness, tingling, or pain. Granchi D, Cenni E, Tigani D, Trisolino G, Baldini N, Giunti A. Correct diagnosis and recommendation for a specific surgical procedure are extremely important for follow-up surgery to ensure that symptoms and spinal instability are truly resolved. Case example. Xie Y, Hu C, Feng Y, Li D, Ai T, Huang Y, et al. Elves MW, Wilson JN, Scales JT, Kemp HB. However, with some individuals and with some types of surgeries, symptoms may arise. [3] Hydrophobic materials have an intrinsic immunogenicity with increased monocyte adhesion. 8th ed. The white blood cell (WBC) count and other assessments of inflammatory mediators (eg, platelet count, C-reactive protein [CRP] level, and erythrocyte sedimentation rate [ESR]) are not elevated or only minimally elevated, and they are not specific or reliable enough to aid in diagnosis. [3] These two groups of cells communicate via cytokines, signaling molecules, transcription factors, and receptors. This example presents a strong possibility of a true metal hypersensitivity reaction. [1], The incidence of metal allergies is rising in the general population, probably as a consequence of increased exposure to metal from piercings, jewelry, and internal medical devices or dental restorations. How do you know if your spouse is not happy? This pain may be felt in the knee itself, or in the surrounding muscles and tissues. 1992. Can a minor go to Mexico without a parent? Biomed Res Int. When implants degrade or corrode, the immune system also responds to surface changes and degradation products. Inorganics include bioactive glass and calcium phosphate. Options for surgical treatment include the following: Revision joint replacement surgery in patients with metal-on-metal prostheses have worse outcomes with more complications when the revision is due to metal reactions [63]. [QxMD MEDLINE Link]. Titanium has the ability to affect lung function causing lung diseases such as pleural disease, it can cause chest pain with tightness, breathing difficulties, coughing, irritation of the skin or eyes. 1977 Oct. 59 (7):862-5. MIF acts to prevent lymphocytes from leaving a site where foreign antigens are present. In the Chicago area, these tests are available at both Loyola University Medical Center and Rush Presbyterian Mecdical Center. Philadelphia: American Society for Testing and Materials; 1992. You are being redirected to Plasma-spray coatings and grouting agents limit exposure and decrease ion release from the implant. 2021 Mar 11. [Full Text]. [QxMD MEDLINE Link]. The signs and symptoms of failure are as follows: Severe and unbearable pain in the operated knee joint. The skin allergic reaction to nickel looks like eczema. 1120700019865530. Traditional blood tests are not useful in the work-up of immune response to implants. Chae et al reported on a coating designed to prevent bacterial adhesion and biofilm formation that is also "immune evasive." [6, 7, 8, 9, 10, 11, 12, 13, 14] ; 17% of women and 3% of men are allergic to nickel, and 1-2% of people are allergic to cobalt, chromium, or both. In patients with suspected titanium hypersensitivity skin prick testing should be considered to confirm the diagnosis if the patch test to titanium is negative. Irrigation and debridement were performed, and the patient was treated with intravenous antibiotics until intraoperative cultures proved negative. [45, 47] : Silver ions are cytotoxic to both bacteria and neutrophils, decreasing the immune response to both the implant and the bacteria. [QxMD MEDLINE Link]. [2], Wettability is strongly associated with protein layer absorption, blood clot formation and fibrin formation. 2014. Composition of common metal alloys used in orthopedic implants. [QxMD MEDLINE Link]. In addition to the percentage of a particular metal contained within an alloy, the nature of the alloy and the local exposure of the implant are important. [QxMD MEDLINE Link]. However, because such a reaction is a diagnosis of exclusion, definitive proof is difficult to achieve. Patients with known nickel allergy who require ORIF of fractures, for example, may be best treated with titanium implants when such devices are available. However, with the large number of joint replacements performed yearly, the largest group of allergic reactions to implants consists of reactions to orthopedic implants. 1993 Jun. WebVery rarely patients develop an allergic reaction to donor bone. WebHowever since surgery and more apparent 8 -10 weeks post surgery are the symptoms of rashing up in area of neck chest throat and site of plate, burning ears and throat, chronic pain in my neck and a feeling of burning and soreness in neck and spine. Can a trust deduct investment advisory fees in 2021? Metal sensitivity is correlated with osteolysis and aseptic loosening of implanted metal hardware. [63], Phase-contrast and laser scan confocal microscopy (LSCM) is another method of quantifying the number of positive cells involved in the immune reaction. [23] The systemic response to deep implants can occur acutely or many years later. 15 (3):173-90. 3:6. [49, 50, 3] Initially, osteoclast activation is important for removal of necrotic tissue and as the first step for bone remodeling around the implant. The discrimination between nickel-sensitive and non-nickel-sensitive subjects by an in vitro lymphocyte transformation test. [24], The issue of the clinical significance of sensitization to implanted metals has long been debated in the literature. [63] The main limitation of this test is that a positive result is not indicative of a true hypersensitivity but must be considered in the context of a patient's medical history and physical findings. Ann Clin Biochem. For example, an MRI study by Galea et al found that cobalt levels in the range of 2.9-3.2 ppb were associated with an increased risk of adverse local tissue reaction in patients who underwent metal-on-metal total hip arthroplasty or hip-resurfacing arthroplasty. 69 (1):62-6. 1994 Mar. Over the ensuing 3 months, the patient's pain increased to an unbearable level. Symptoms of body rejecting surgical hardware jobs [QxMD MEDLINE Link]. 7 (3):233-245. [QxMD MEDLINE Link]. Veien NK, Svejgaard E, Menn T. In vitro lymphocyte transformation to nickel: a study of nickel-sensitive patients before and after epicutaneous and oral challenge with nickel. 2015 Dec. 98 (6):953-62. 75 (6):799-801. The patient had positive nickel sensitivity, as shown on both skin patch testing and lymphokine MIF testing, and negative culture results with no clinical evidence of infection. symptoms of body rejecting surgical hardware Materials (Basel). Expert Rev Med Devices. The immune response to an implant can either be a true systemic hypersensitivity reaction or be caused by local damage from the implant. [5] It is common for metal hypersensitivity to present as a skin rash at the site of the implant, An infection can occasionally be the cause of pain as well, so your surgeon will evaluate patients for this potential problem. Hypersensitivity reactions to metal implants: laboratory options. [5] Testing may also be indicated for patients in whom infection and mechanical factors have been ruled out as the cause of implant failure or for patients with localized rash, pain, swelling, or inflammation near or over the implant or systemic cardiac or neurologic symptoms. Sensitivity to implant materials in patients with total knee arthroplasties. [QxMD MEDLINE Link]. Moisturize regularly. Allergy, Principles and Practice. However, local symptoms, squeaking, or high acetabular version or inclination may also indicate the need for advanced imaging. Symptoms of body rejecting surgical hardware Metal hypersensitivity in total hip and knee arthroplasty: Current concepts. [2, 3] Future implant design may depend on the relatively new specialty of osteoimmunology, with a shift in emphasis from immune "evasion" to immune "reprogramming." If this is not acceptable for symptom relief, then consideration should be given to removing the hardware after the fracture or fusion has fully healed. Park HS, Nakagawa I, Yokoyama S, Wajima D, Wada T, Motoyama Y, et al. Both involve a robust intra-articular immune response; however, metal reaction shows predominance of perivascular lymphocytes, plasma cells, and macrophages, whereas infection is characterized by an abundance of neutrophils on biopsy. J Bone Joint Surg Am. [QxMD MEDLINE Link]. [QxMD MEDLINE Link]. Cystic changes, such as occur in osteolysis, may be seen (see the image below). Middleton's Allergy: Principles and Practice. symptoms of body rejecting surgical hardware Cell culture methods for testing biocompatibility. Late onset infection can occur in some cases where you have some focus of infection causing bacteremia,and the sign symptoms include, redness. [3, 2]. Rejection Acrylic bone cement and its polymerization additives (benzoyl peroxide and N,N-dimethyl-p-toluidine) can cause severe hypersensitivity reactions in total knee arthroplasty. [63] as a rule, testing can be considered in patients with known hypersensitivity reactions. 2007 Dec. 28 (34):5044-8. Available at https://www.sciencedaily.com/releases/2014/10/141009153817.htm. Clin Oral Implants Res. 2017. [64, 65, 13, 5] A positive result can occur in completely asymptomatic patients. Donati ME, Savarino L, Granchi D, Ciapetti G, Cervellati M, Rotini R, et al. Perivascular and diffuse lymphocytic inflammation are not specific for failed metal-on-metal hip implants. They can range from mild to severe and develop shortly after contact with gold or a long-time wearing. 2009 Jan. 5 (1):172-80. If they use your own bone your body should not react to it. Immune Response to Implants and Biomaterials, encoded search term (Immune Response to Implants and Biomaterials) and Immune Response to Implants and Biomaterials, Conduits for Vascular Reconstruction in the Pediatric Patient. [QxMD MEDLINE Link]. 1979. 2022 - 2023 Times Mojo - All Rights Reserved Teo Wendy ZW, Schalock PC. May 15, 2013; Accessed: April 5, 2022. Certain foot and ankle operations have a higher rate of needing hardware removal than others. Skin patch testing may therefore be unreliable. [5, 6, 17, 18, 19] It is thought that the immune system may become sensitized to the presence of a metal implant with a resultant increase the incidence of positive skin testing, though it is unclear how often this response is pathologic. 20 (2):89-94. Some patients also complain of achiness in the foot or ankle related to weather changes. Biomaterials. Ital J Orthop Traumatol. Other Santavirta S, Konttinen YT, Bergroth V, Grnblad M. Lack of immune response to methyl methacrylate in lymphocyte cultures. William J Hopkinson, MD, FACS, FAAOS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Society for Sports Medicine, Illinois Association of Orthopaedic Surgeons, Illinois State Medical SocietyDisclosure: Nothing to disclose. Painful Hardware is a possible side effect from metal screws and plates, which are often used in surgery to fix fractures, fuse joints, or stabilize bones. All material on this website is protected by copyright, Copyright 1994-2023 by WebMD LLC. The body can reject plates and screws as your body has no material, but titanium as a biomaterial for implants and PEEK is safe and has few complaints so far. [QxMD MEDLINE Link]. [Full Text]. 61-70. Significantly increased cytokine levels are found in patients with aseptic loosening of implants in comparison with levels at the initial surgical procedure. swelling. 14 (6):[QxMD MEDLINE Link]. Markel D, Bou-Akl T, Rossi M, Pizzimenti NM, Wu B, Ren WP. Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration. Brown SA, Merritt K, Mayor MB. [2, 49]. Also, the results depend on the experience of the person visually reading the skin reaction and may be influenced by medications, the quality of the antigens chosen, and the time of reading. [10, 18, 21] others have argued that even if a metal allergy exists, no adverse effects occur. What is the average woman's engagement ring size? [2]. 2021 Jul. Whittingham-Jones PM, Dunstan E, Altaf H, Cannon SR, Revell PA, Briggs TW. Patients with metal-on-metal implants should be monitored for metal ion levels at intervals of 6-12 months. The symptoms or signs of a rejected implant can be: systemic, meaning symptoms affecting the whole body; or; localized, meaning the affected area is limited to the area where the hernia mesh surgery was conducted (or the incision site). for: Medscape. [61]. Stimulation of T cells to secrete highly immunosuppressive cytokines (eg, IL-17) may promote tolerance of implants. 2020 Jun. J Clin Orthop Trauma. [3] M1 proinflammatory macrophages arrive as part of the initial inflammatory response Dermatitis. For patient education resources, see Total Hip Replacement and Knee Joint Replacement. Corrosion and Degradation of Implanted Materials: Second Symposium. [2] This matrix is rich in growth factors, cytokines, and matrix metalloproteinases, which promote the immune response and recruit neutrophils. In the meantime, the orthopedic surgeon must be aware of the potential problem but should exercise caution in making the diagnosis. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug ReferenceDisclosure: Received salary from Medscape for employment. Koutalos AA, Toms AP, Cahir JG, Smith EJ. Traditionally, skin patch testing has been the standard screening test for metal hypersensitivity; it is cost-effective and technically simple. 24 (1):25-36. Lachiewicz PF, Watters TS, Jacobs JJ. 1980 Oct. 1 (4):193-8. Svejgaard E, Morling N, Svejgaard A, Veien NK. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2001. 469 (4):1127-33. Considerations of allergy and mechanics in the selection of orthopaedic implant materials [proceedings]. Memory T helper cells identify patients with nickel, cobalt, and chromium metal allergy. However, patients with known symptomatic metal allergies do have poorer results. Skin-patch testing or lymphocyte transformation testing (LTT), when the patch test result is questionable, prior to revision knee or hip replacement has been recommended, despite the limitations [63] A radioactive marker (3H-thymidine) is added to lymphocytes along with the desired challenge agent. [46] Antimicrobial peptide coatings, besides their direct action against microorganisms, may also exert an immune-regulatory effect by decreasing the immune response to the implant, resulting in osteointegration/bone formation around the implant. [45, 15] but, paradoxically, can also provoke an immune response to the coating substances themselves. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. [QxMD MEDLINE Link]. ScienceDaily. In a study including 11 cases where periprosthetic tissue contained corrosive elements (solid chromium orthophosphate corrosion products) after aseptic loosening of articular implants, immune-response tissue reactions were identified in every case. Do Men Still Wear Button Holes At Weddings? [QxMD MEDLINE Link]. sores and swelling in the soft tissues of the mouth. Immune responses in patients with metal-on-metal hip articulations: a long-term follow-up. Wear particles, periprosthetic osteolysis and the immune system. 1977. Before routine total hip or knee replacement in patients suspected of having metal allergies, alternative prostheses may also be indicated, including ceramic implants, implants composed of different alloys, and coated implants These objects are generally not seen on x-ray (radiolucent). Patients can present with localized dermatitis or rashes but also with systemic eczematous dermatitis. It involves measuring the proliferative response of T lymphocytes after activation. Case example. Hallab N, Jacobs JJ, Black J. Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays. The hardware was not loose, and the fracture was stable and clinically healed. New blood test finds allergies BEFORE implant surgery. Surface roughness promotes positive cytokine secretion and improves immune cell adhesion. Lymphocyte transformation induced by nickel sulphate: an in vitro study of subjects with and without a positive nickel patch test. Acta Biomater. 2008 Feb 13. Is it unhealthy to sit on the toilet too long? [5] It therefore is not surprising that immune response to medical implants is commonly reported in the literature, including hypersensitivity to pacemakers or other cardiovascular devices, endovascular stents and coils, dental implants, and orthopedic hardware (eg, joint replacement prostheses, fracture fixation devices, and pain-relief stimulators). Clin Orthop Relat Res. Response profiles of circulating leukocytes and metal ions in patients with a modular dual-mobility hip implant. Knopf-Marques H, Singh S, Htwe SS, Wolfova L, Buffa R, Bacharouche J, et al. Why Do Cross Country Runners Have Skinny Legs? Polyelectrolye multilayer films from hyaluronic acid have been developed, with good early experimental results. Case example. [40] At present, the published data are insufficient to determine safe reference ranges for blood levels of cobalt and chromium, but in the unexposed population, normal ranges are below 10 nmol/L and below 5 nmol/L, respectively. 85 (1):7-16. [Full Text]. The following tests are more difficult to obtain because many clinical laboratories do not run them. [QxMD MEDLINE Link]. [48] , leading to inflammation that activates macrophages as part of the inflammatory cascade. [4], In light of these contradicting studies, it is difficult for the orthopedic surgeon to make the diagnosis of symptomatic metal allergy with confidence. [QxMD MEDLINE Link]. [QxMD MEDLINE Link]. Patients with joint replacements typically have symptoms of loosening, including pain and instability. It may also be done when the hardware causes allergy or bone fracture. Contact Dermatitis. Radiography demonstrated loosening and cutout of the hip lag screw, but the fracture was healing (see the image below). [QxMD MEDLINE Link]. Acta Derm Venereol. According to the National Institute of Health, allergic symptoms resulting from exposure to metals typically appear 24 to 48 hours after exposure. In this instance, symptoms can be treated with local padding, such as wearing a thick sock or using a local gel pad. When patients are recovering from the original injury or surgery, the symptoms and swelling are such that the hardware is usually not a significant issue. I have the same issue going on in my back! They can do a hardware injection into your back around the hardware, if this gives you relief then they 2016 Nov 23. Gallo J, Holinka M, Moucha CS. MRI scans are rarely useful for painful metal implants since metal causes artifact, which prevents visualization of neighboring tissues, or even the entire foot. Apply wet compresses, which can help dry blisters and relieve itching. 2021 Oct. 11:20-24. Signs and symptoms include an itchy rash with redness, swelling, scaling and possibly a crusty appearance. 15:7. They use this type of metal because it is the least 1979 Jan. 5 (1):27-32. The symptoms can be due to a screw or plate that rubs against a boot, or pain may be produced when the tendon or soft tissue structure rubs against the prominent screw or plate. 4 (13):2026-36. Monitoring chromium and cobalt concentrations has been suggested for all patients with metal-on-metal hip replacement bearing surfaces, but particularly for those who are symptomatic. Albrektsson T, Becker W, Coli P, Jemt T, Mlne J, Sennerby L. Bone loss around oral and orthopedic implants: An immunologically based condition. Swiontkowski MF, Agel J, Schwappach J, McNair P, Welch M. Cutaneous metal sensitivity in patients with orthopaedic injuries. The effects of metal corrosion debris on immune system cells. [QxMD MEDLINE Link]. Although this article focuses primarily on immune responses in patients with already implanted orthopedic devices, it is also worthwhile to note that prevention of the pathologic reaction to an implant, by choosing alternative prostheses or fracture fixation implants during preoperative planning, should be considered in selected patients with known metal hypersensitivity. After an implant is placed, a complex immune cascade follows that can lead to the following two possible outcomes, depending on the design of the implant Arthroplast Today. Int J Mol Sci. Titanium, molybdenum, and cobalt have low toxicity as compared with nickel and chromium, which can cause highly toxic intracellular changes. At 4-year follow-up, she had no further complaints or problems (see the second image below). Physical signs of implant failure (popping, squeaking or pain in the hip). J Am Acad Orthop Surg. 2012 Jun. Merritt K, Brown SA. Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings. 1994. Br J Dermatol. Atanaskova Mesinkovska N, Tellez A, Molina L, Honari G, Sood A, Barsoum W, et al. [50], The switch from M1 to M2 is regulated by immune cells, including T cells of various subsets, cytokines, and microRNAs (miRNAs). First, make sure your jewelry is made of 14k, 18k, or 24k yellow gold or rose gold. [2, 3] A consistently elevated M1 response with a decreased or absent M2 response causes chronic inflammation, delayed tissue healing, and failure of biomaterial integration. Swelling, pain, draining sinuses, and inflammation at the implant site may mimic infection. [74, 75, 76], The few investigations using the LTT have reported that increased rates of metal sensitivity can be detected above what can be determined by means of dermal patch testing. 2020 Jan. 30 (1):64-70. [2] : An immune response always occurs. If it remains clear, the item has no free nickel and will not cause dermatitis. 1977 Oct. 38 (2):67-8. [32], The test is performed by obtaining a blood sample and isolating the lymphocytes. TimesMojo is a social question-and-answer website where you can get all the answers to your questions. The metals most commonly reported with positive preoperative skin test results before revision knee or hip replacement where metal hypersensitivity is diagnosed are nickel (52%), palladium (32%), gold (23%), and cobalt (19%); patients may be allergic to more than one metal. The confusion is a result of the presence of different metals in the implants, different manufacturing methods, small numbers of patients in the studies, nonspecific testing modalities, and a lack of definitive clinical guidelines for making the diagnosis. 2018 Jan. 10 (1):e1. Surveillance of Patients with Metal-on-Metal Hip Resurfacing and Total Hip Prostheses: A Prospective Cohort Study to Investigate the Relationship Between Blood Metal Ion Levels and Implant Failure. Particulate Debris From Medical Implants. 2013 Jul-Aug. 24 (4):183-5. [50], An online study by Mesinkovska showed thatpreoperative skin patch testing for metal allergy changed treatment in 68% of 31 patients undergoing revision total joint replacement. Carl N Graf, MD is a member of the following medical societies: American Medical AssociationDisclosure: Nothing to disclose. [3] IL-10 is an anti-inflammatory cytokine that has a significant role in maintaining immune homeostasis and resolving inflammation. 2008 Apr. An allergic reaction could occur at a most inopportune time. [4] Bone cement hypersensitivity can be challenging, and revision using cementless procedures does not guarantee relief of presenting symptoms. Radiolucencies around the hardware, screw migration, and changedposition of the implant imply loosening that could be due to hypersensitivity to the metal or could be the catalyst that induces a robust immune response. [QxMD MEDLINE Link]. Pain around the site of orthopedic implants has many causes, and before blame can be assigned to metal sensitivity or allergy, a thorough investigation must occur. Local inflammatory symptoms similar to the symptoms of infection are also possible, including warmth, erythema, and swelling over the implant, though systemic complaints (eg, fever) are unlikely. Pain when you first get up to walk can also be a concern. Lymphocyte transformation in vitro in dermatophytosis. Which Teeth Are Normally Considered Anodontia? 2008 Aug. 19 (8):823-35. [38, 5, 39]. [4] Screening itself may induce sensitization. [2], Surface charge changes the immune response. [39] However, it is important to note that as many as 20% of periprosthetic joint infections are culture-negative.