Nickel allergy does not correlate with function after total knee arthroplasty.

PURPOSE: The purpose of this study is to determine if there is a relationship between clinical outcomes and nickel allergy by evaluating asymptomatic total knee arthroplasty (TKA) patients with well-functioning implants through quantitative metal allergy (MA) testing. METHODS: A prospective case series was performed on 50 patients with well-functioning TKA of various implant types. Inclusion criteria included primary TKA with a minimum 12-month follow-up and Oxford knee score (OKS) ≥ 40. A commercially available Lymphocyte Transformation Test measured the amount of a hypersensitivity lymphocyte immune response after exposure to a particular antigen. MA results were stratified based on the stimulation index (SI). The Cochran-Mantel-Haenzel test was used to test the homogeneity of metal reactivities. The Wilcoxon-Mann-Whitney test was used to compare individual metal SI by gender and the association of OKS and metal SI was ascertained with the Spearman correlation. RESULTS: Nickel, cobalt, and chromium do not have the same reactivity scores (p < 0.001), and only nickel showed reactive/highly reactive scores. Females were found to have 3.41 times the odds of males for higher Ni reactivity (p = 0.0295, odds ratio [OR], 95% confidence interval [CI] = 3.41 [1.13-10.3]) only. Clinically, there was no correlation between metal SI and OKS score by metal (Ni rho = -0.1779; Co rho = -0.0036; Cr rho = -0.1748). CONCLUSION: This is the first study looking at MA in well-functioning TKA. There is no correlation between clinical results and nickel reactivity. Surgeons should exercise caution when revising a painful or poorly functioning TKA based solely on a 'positive' Nickel Allergy test and look for other possible reasons for failure. LEVEL OF EVIDENCE: Level II.

Understanding immune-mediated titanium allergy to in situ orthopaedic implants: a narrative review of the current literature.

INTRODUCTION: Clinical recognition of potential immune-mediated allergic responses to implanted metal devices is increasing. For orthopaedic implants, while 'pure' compounds are used in specific circumstances, the majority of components are alloys - a combination of two or more distinct metals. Titanium is found commonly in many orthopaedic devices and is often championed as a 'hypoallergenic' option or inclusion. In the absence of a relevant previously published summary on the topic, this paper explores the current state-of-understanding of titanium allergy and proposes a patient management algorithm whereby such immune reactions are clinically-suggested. METHODS: A structured, systematic literature review was performed following PRISMA search principles to provide a contemporary summary-of-understanding in this area and to highlight clinical and knowledge deficiencies. RESULTS: Thirty-five topic-related articles were identified, the majority reflecting small case series' or proof-of-concept studies. The general standard of scientific evidence available was poor. Justification for arthroplasty utilization of titanium as a 'hypoallergenic' option is largely extrapolated from non-orthopaedic domains. CONCLUSIONS: Both ionic and conjugated titanium particles released from implant surfaces have the potential to trigger innate immune responses and true allergy. There exists no simple, high-sensitivity, screening test for titanium allergy. Conventional skin-patch testing is unreliable due to poor dermal penetration. Given established lymphocyte and macrophage activation pathways for allergy responses, in vitro methods using both cell-types show diagnostic promise. Surgical biopsy analysis from host-implant interfaces remains the contemporary 'gold-standard', however this represents an invasive, costly and highly-specialized approach not readily available in most settings. Further research to establish reliable/accessible diagnostic methods are indicated.

Less efficient skin penetration of the metal allergen Pd2+ compared to Ni2+ and Co2+ from patch test preparations.

BACKGROUND: Contrary to Ni2+- and Co2+-induced allergic contact dermatitis (ACD), reactions against Pd2+ are rare. However, Pd2+ activates a larger T cell fraction in vitro, suggesting an inefficient skin penetration. OBJECTIVES: This study compares Ni2+, Co2+ and Pd2+ skin penetration from commonly used diagnostic patch test preparations (PTPs) and aqueous metal salt solutions. METHODS: Using Franz diffusion cell assays, we applied the metals in PTPs (5% NiSO4, 1% CoCl2, 2% PdCl2 and 3% Na2PdCl4) and in solution to pigskin for 48 h, thereby mirroring the time frame of a patch test. The different compartments were analysed individually by inductively coupled plasma mass spectrometry. RESULTS: Metal ions were mainly retained in the upper stratum corneum layers. After application of PTPs, concentrations in the viable skin were lower for Pd2+ (1 and 7 µM) compared to Ni2+ and Co2+ (54 and 17 µM). CONCLUSIONS: Ni2+ and Co2+ penetrated the skin more efficiently than Pd2+ and thus may sensitize and elicit ACD more easily. This was observed for ions applied in petrolatum and aqueous solutions. We hypothesize that the differently charged metal complexes are responsible for the varying skin penetration behaviours.

Dietary Intervention for Control of Clinical Symptom in Patients with Systemic Metal Allergy: A Single Center Randomized Controlled Clinical Study.

Patients with eczema with a systemic metal allergy, such as nickel (Ni), cobalt (Co), chromium (Cr), and tin (Sn), should pay attention to symptomatic exacerbation by excessive metal intake in food. However, dietary intervention for systemic metal allergy can be difficult. In this study, we evaluated the effect of dietary intervention by a registered dietitian on clinical symptoms in patients with a systemic metal allergy. Forty-four patients with cutaneous symptoms who were diagnosed with a metal allergy were randomly assigned to the dietary intervention group (DI group, n = 29) by a registered dietitian or the control group (C group, n = 15). The DI group was individually instructed by a registered dietitian how to implement a metal-restricted diet and then evaluated 1 month later. Dermatologists treated skin lesions of patients in both groups. Skin symptoms assessed by the Severity Scoring of Atopic Dermatitis (SCORAD) index, blood tests, and urinary metal excretion were evaluated. The DI group showed decreased Ni, Co, Cr, and Sn intake (all P ≤ 0.05), and an improved total SCORAD score, eczema area, erythema, edema/papulation, oozing/crust, excoriation, lichenization and dryness after 1 month of intervention compared with before the intervention (all P ≤ 0.05). However, the C group showed decreased Ni and Sn intake and an improved oozing/crust score (all P < 0.05). It showed the effective reduction of dietary metal intake controls dermatitis due to a metal allergy. In conclusion, dietary intervention by a registered dietitian is effective in improving skin symptoms with a reduction in metal intake.

Hypersensitivity to metals in metal-on-metal hip arthroplasty: a prospective study of one hundred and thirty five lymphocyte transformation tests.

BACKGROUND: Metal allergy remains a controversial topic in the orthopaedic community. It is not known if or to what degree metal sensitivity contributes to inflammatory soft tissue failures, unexplained residual pain, or clinical complications after total joint replacement with metal prostheses. METHODS: We investigated the efficacy of the lymphocyte transformation test (LTT) in predicting adverse outcomes in patients after receiving a metal joint replacement. Our study cohort consists of 135 metal-on-metal hip resurfacing arthroplasty cases performed between 2013 and 2015. All study patients had an LTT preoperatively. We retrospectively analyzed clinical outcomes and failures for our cohort. RESULTS: There was no difference in LTT reactivity between men and women. Of the 135 patients tested, 46 (34.1% of cohort) tested positive to at least one of the materials comprising their implant, and 78 patients (57.8%) had at least one reactive score to any component of the LTT. After a minimum follow-up of two years, we did not observe an allergic response to the implant in any patients. There were no failures requiring revision. We observed a 2.2% rate of moderate residual pain; no patients with residual pain tested positive for metal sensitivity. When patients with moderate-high LTT reactivity (30.4% of cohort) were compared to the remainder of the study group, there was no difference in HHS or UCLA activity score. There was no correlation between blood metal ion levels and LTT reactivity. CONCLUSION: We were unable to prove any predictive value of the LTT. We failed to identify hypersensitivity to metals in patients with metal-on-metal hip resurfacing arthroplasty.

Preoperative Metal Allergy Testing for Pectus Excavatum Repair Does Not Effectively Identify Patients Who Develop Metal bar Allergy.

BACKGROUND: Metal allergy following placement of a metal pectus bar for minimally invasive repair of pectus excavatum (MIRPE) is a rare complication with potentially significant morbidity. There is no consensus regarding preoperative metal allergy testing (MAT). This study aims to assess incidence of metal allergy and titanium bar use in tested and untested patients and trends in MAT with different approaches to MAT. METHODS: A retrospective chart review was performed on patients who underwent MIRPE from July 2009 to June 2022 at a single institution. During this time, MAT was performed routinely (RT; routine testing) and selectively (ST; selective testing). RESULTS: The cohort included 741 patients for analysis. Metal bar allergy was documented in 1.3 % of all patients; the incidence was 1.3 % in patients with MAT and 1.4 % without MAT. The incidence of bar allergy was 1.1 % in the RT group and 1.6 % in the ST group. In the RT group, bar allergy occurred in 1.4 % (3/216) of patients with a negative MAT. In the ST group, bar allergy occurred in 1.2 % (2/164) of patients with a negative MAT and in 1.9 % (3/162) of untested patients with a stainless-steel bar. Titanium bar use was not significantly different between the RT and ST groups (18.3 % vs 16.3 %, p > 0.05). CONCLUSION: The incidence of metal bar allergy after MIRPE was less than 2 %, and titanium bar use was not significantly different in routine and selective testing groups. MAT was not associated with a reduction in bar allergy, and its use remains unsupported. LEVEL OF EVIDENCE: III.

Do Patients With Hypoallergenic Total Knee Arthroplasty Implants for Metal Allergy Do Worse? An Analysis of Health Care Utilizations and Patient-Reported Outcome Measures.

BACKGROUND: Metal allergy is a rare and controversial cause of implant failure and poor outcomes following total knee arthroplasty (TKA). Few studies have investigated clinical and patient-reported outcome measures (PROMs) in patients treated with hypoallergenic implants. This investigation aimed to compare: (1) health care utilizations (eg, hospital length of stay, 90-day readmission rate, and incidence of nonhome discharge) and (2) 1-year PROMs between patients who received hypoallergenic and standard TKA implants. METHODS: This was a retrospective review of prospectively collected data from patients who underwent primary TKA between 2018 and 2019. Propensity score matching (3:1) was used to compare standard TKA patients with those who received hypoallergenic TKA implants, respectively. Knee injury and Osteoarthritis Outcome Score (KOOS) pain, KOOS Physical function Shortform (PS), and Veterans RAND 12-Item Health Survey Mental Component Score were collected preoperatively and at 1-year. After matching, 190 hypoallergenic and 570 standard TKAs were analyzed. RESULTS: No differences were observed in length of stay (P = .98), 90-day readmission (P = .89), and nonhome discharge (P = .82). Additionally, there was no significant difference in change from preoperative to 1-year PROMs (KOOS pain, P = .97; KOOS PS, P = .88; Veterans RAND 12-Item Health Survey Mental Component Score, P = .28). Patient-reported satisfaction was similar at 1-year (P = .23). Patients achieved similar rates of Patient Acceptable Symptom State (PASS) and minimal clinically important difference (MCID) for KOOS pain (PASS, P = .77; MCID, P = .33) and KOOS PS (PASS, P = .44; MCID, P = .65). CONCLUSION: Patients treated with hypoallergenic TKA implants for suspected metal allergy had similar outcomes compared to patients who had standard implants and no metal allergy.

The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies.

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.

Skin Symptoms That Appeared after Fixation with a Titanium Plate in a Jaw Deformity Patient Suffering from Palmoplantar Pustulosis: A Case Report.

Palmoplantar pustulosis (PPP) is a stubborn skin disease involving repeated aseptic small pustules on the palms and soles of the feet, which is triggered and exacerbated by metals and dental focal infections. There are few reports of an exacerbation of PPP symptoms after orthognathic surgery. The patient is a 40-year-old female who consulted an orthodontist at our hospital, complaining of a protruding maxilla and malocclusion. Under the diagnosis of skeletal prognathism, she underwent surgery for jaw deformity. Although no allergic symptoms were observed during the orthodontic treatment prior to surgery, postoperative scaling on the palms and soles of her feet worsened, and itching was observed on the skin, especially on the titanium plate used to secure the bone fragments. Under the diagnosis of metal allergy, treatment with steroids and vitamin D ointment failed to improve the condition, so surgery was performed to replace the metal plate with a non-metallic absorbable plate in the third postoperative month. Afterwards, the pruritus resolved, and erythema and scale on the palms and soles nearly disappeared. In the present case, though, oral bacterial infection, a past history of smoking, and stress from surgery were also considered to be possible causes of PPP exacerbation, and we concluded that one of the causes of PPP exacerbation was metal allergy from the plates or screws used to fix the bone fragments.

Stability of ceramic coatings on retrieved knee prostheses.

BACKGROUND: In total knee arthroplasty, femoral components with coated or oxidized surfaces are commonly used as alternative to CoCrMo in metal sensitive patients. Data on the in vivo behaviour of different coating types is, however, rare. Aim of the study was the investigation of coating stability with respect to implant and patient specific parameters. METHODS: Coating thickness and coating thickness reduction, respectively, was measured at 37 retrieved femoral components with TiNbN, TiN, ZrN or oxidized zirconium (OxZr) surface by the crater grinding method. The results were correlated to surface type, manufacturer, time in vivo of the implant, patient body weight and patient activity. RESULTS: Mean coating thickness reduction in the overall retrieval collection was 0.6 µm ± 0.8 µm. There was no correlation between coating thickness reduction and coating type, time in vivo, patient body weight, and patient activity. If grouped according to manufacturers, implants of one manufacturer showed an increased coating thickness reduction. 10 of 37 retrievals exhibited coating abrasion with exposure of the underlying alloy. TiNbN coatings showed the highest incidence (9/17) of coating abrasion. No coating breakthrough was observed in the ZrN or OxZr surfaces. CONCLUSION: Our results indicate that TiNbN coatings should be optimized to improve their wear resistance in the long-term.

Reversible and multiphasic parenchymal changes in MRI after coil embolization for a ruptured cerebral aneurysm.

Background: Reversible and multiphasic parenchymal changes in magnetic resonance imaging (MRI) are exceedingly rare. The authors experienced a case of reversible and multiphasic parenchymal changes in MRI after coil embolization for a ruptured cerebral aneurysm. Case Description: A 48-year-old woman had a sudden onset of severe headaches and was referred to us for coil embolization. She was alert-oriented and had no neurologic deficits. Her medical history was atopic dermatitis and metal allergy. A head computed tomography (CT) scan demonstrated subarachnoid hemorrhage, and three-dimensional-CT angiography revealed a left internal carotid artery-posterior communicating artery aneurysm. Coil embolization was performed on the next day and seven coils made by three different manufacturers were used for the embolization. Despite no neurologic deficits after the surgery and no abnormal findings in MRI 7 days after the coil embolization, an MRI 2 weeks after embolization demonstrated delayed multiple white matter high intense lesions on T2-weighted image and fluid-attenuated inversion recovery in the left hemisphere. Repeat MRI scans showed multiple high intense lesions at various locations and at different timings. The blood test revealed the elevation of the proportion of EOS up to 9.7%, strongly indicating some allergic response. The MRI scan obtained 3 months after the onset confirmed the complete disappearance of the lesions. Conclusion: Given her history of metal allergy, and the reversible and multiphasic lesions in the non-vascular territories of the treated aneurysm, metal allergic encephalitis was most likely despite no clear evidence.

Metal Hypersensitivity Following Total Ankle Arthroplasty: Case Series and Literature Review.

Metal hypersensitivity following total ankle arthroplasty (TAA) is an underreported complication that can manifest as dermal, systematic, and orthopaedic-specific symptoms. It is critical to recognize that metal hypersensitivity is a diagnosis of exclusion; only after all other potential sources of failure, such as loosening or infection are ruled out, can this diagnosis be considered. Aside from imaging and common laboratory analysis, skin patch testing, leukocyte migration inhibition test (LMIT), and lymphocyte transformation test (LTT) are the testing options available for metal allergy. With regards to management of metal hypersensitivity, nonoperative modalities involving topical dermatological management are generally preferred. Severe cases of metal allergy may necessitate operative management consisting of explantation of the implant and either revision TAA with a custom hypoallergenic implant or conversion to an ankle fusion. We present 3 cases of presumed metal hypersensitivity following TAA. In all 3 cases, other forms of TAA failure were carefully ruled out. One patient underwent explantation and conversion to hypoallergenic implant, 1 patient underwent explantation and ankle arthrodesis with hypoallergenic hardware, and 1 patient elected for conservative care. In patients who underwent explantation and conversion to hypoallergenic hardware, no further symptoms associated with metal allergy were noted. Additional research is necessary to improve diagnostic accuracy of metal allergy and make treatment options more effective and accessible.Level of Evidence: Retrospective case series, IV.

A Comparison of Clinical Outcomes After Total Knee Arthroplasty in Patients With Preoperative Nickel Allergy Receiving Cobalt Chromium or Nickel-Free Implant.

BACKGROUND: The role of metal hypersensitivity reactions in total knee arthroplasty (TKA) failure is debated. There is no consensus on whether use of a more expensive nickel-free implant is indicated for patients who have preoperative nickel allergy. The purpose of this study was to examine the outcome of patients who have preoperative nickel allergy receiving nickel-free or cobalt chromium (CoCr) implants. METHODS: This was a retrospective review of 17,798 patients who underwent 20,324 unilateral primary TKAs between 2016 and 2020. Presence of preoperative nickel allergy was determined (n = 282). Patients were divided into 2 cohorts: those receiving (1) nickel-free or (2) CoCr implants. Clinical outcome scores and revision rates were assessed. RESULTS: 243 received a nickel-free implant and 39 received a CoCr implant. There was no significant difference in revision rate between the cohorts. Survivorship free of revision was 94% in the CoCr implant cohort and 98% in the nickel-free implant cohort (P = .9). When comparing clinical outcome scores between cohorts, there was no difference in preoperative, 6-week or 1-year Knee Osteoarthritis Outcome Score Joint Replacement, Visual Analog Scale (VAS), Lower Extremity Activity Scale, Patient-Reported Outcomes Measurement Information System (PROMIS), and Veterans RAND 12-item scores between cohorts. CONCLUSION: In this retrospective cohort study, there was no difference in revision rates or clinical outcomes in patients who had a nickel allergy undergoing primary TKA with CoCr or nickel-free implants. Further studies are needed to determine if nickel allergy is an independent risk factor for worse TKA outcomes in general.

Identification of microRNA Signatures in Peripheral Blood of Young Women as Potential Biomarkers for Metal Allergy.

MicroRNA (miRNA) is a short (19-24 nucleotide) endogenous non-protein RNA that exists in the body and controls the translation process from genes to proteins. It has become useful as a diagnostic tool and a potential treatment target in cancer research. To explore the function of miRNA in contact dermatitis, female participants with a positive metal allergy diagnosis (n = 3) were enrolled along with additional female participants with no medical history of metal allergy (n = 3). A patch test was performed on each participant. Peripheral blood was collected from all the participants before the patch test and at days 3 and 7 after starting the patch test. After total RNA was obtained from peripheral blood leukocytes and cDNA was generated, microarray analysis was performed to analyze the large-scale circulating miRNA profile. Real-time polymerase chain reaction (RT-PCR) was then used to clarify the overall target miRNA expression. Downregulation of hsa-let-7d-5p, hsa-miR-24-3p, hsa-miR-23b-3p, hsa-miR-26b-5p, and hsa-miR-150-5p was found on day 7. Certain miRNAs were confirmed using RT-PCR. These peripheral blood miRNAs could be diagnostic biomarkers for metal allergies.

No clinical difference at mid-term follow-up between TiN-coated versus uncoated cemented mobile-bearing total knee arthroplasty: a matched cohort study.

INTRODUCTION: Nitride-based ceramic coating was introduced into surgical implants to improve hardness, reduce abrasion, and decrease the risk of metal-induced adverse reactions, especially for patients with suspected or identified metal hypersensitivity. The study aimed to evaluate the effectiveness and safety of a titanium nitride (TiN) coated prosthesis with a mobile bearing design. METHODS: This was a retrospective matched-cohort study from a single center, comparing clinical outcomes between patients receiving either a TiN-coated versus an uncoated cobalt-chromium-molybdenum (CoCrMo) prostheses for primary total knee replacement. Seventeen patients received the TiN prosthesis between 2015 and 2019. These were matched 1:2 with patients receiving uncoated mobile-bearing knee prostheses with the same design manufacturer. RESULTS: Fourteen patients in the TiN group had complete 5-year follow-up data and were compared with 34 patients from the CoCrMo group. The Knee Society Score was 170.6 ± 28.0 (Function subscore 83.7 ± 17.5 and Knee subscore 86.9 ± 13.8) in the TiN group and 180.7 ± 49.4 (Function subscore 87.5 ± 14.3 and Knee subscore 93.2 ± 9.6) in CoCrMo group, with no statistically significant difference (p = 0.19). One patient underwent a revision for instability requiring the removal of the implant in the TiN group and none in the CoCrMo group. The survival rates were 92.9% (CI95% 77.3-100.0) and 100.0% in the TiN group and CoCrMo group respectively (p = 1.0). DISCUSSION: TiN-coated TKA with mobile bearing resulted in satisfactory clinical outcomes, and a low revision rate, and there was no complication related to the coated implant. The use of TiN-coated prostheses in case of confirmed or suspected metal allergy provides satisfactory short-term clinic outcomes.

Characterization of Metal-Specific T-Cells in Inflamed Oral Mucosa in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis.

The element chromium (Cr) is a component of several types of alloys found in the environment, or utilized in dentistry, that may cause intraoral metal contact allergy. However, the pathological mechanism of intraoral Cr allergy remains unclear because there is no established animal model of Cr allergy in the oral mucosa. In this study, we established a novel murine model of Cr-induced intraoral metal contact allergy and elucidated the immune response in terms of cytokine profiles and T-cell receptor repertoire. Two sensitizations with Cr plus lipopolysaccharide solution into the postauricular skin were followed by a single Cr challenge of the oral mucosa to generate the intraoral metal contact allergy model. Histological examination revealed that CD3+ T-cells had infiltrated the allergic oral mucosa one day after exposure to the allergen. The increase in T-cell markers and cytokines in allergic oral mucosa was also confirmed via quantitative PCR analysis. We detected Cr-specific T-cells bearing TRAV12D-1-TRAJ22 and natural killer (NK) T-cells in the oral mucosa and lymph nodes. Our model demonstrated that Cr-specific T-cells and potent NKT-cell activation may be involved in the immune responses of Cr-induced intraoral metal contact allergy.