Titanium cutaneous metallosis after reverse total shoulder arthroplasty

Abstract

Metallosis is the accumulation of metallic particulates and ions in the soft tissues surrounding a metallic implant. Mechanical abrasion of metallic joint prostheses generates particulate debris, which may be responsible for local inflammatory reaction with tissue discoloration, followed by aseptic soft tissue necrosis or masses (pseudotumors), as well as aseptic osteolysis and implant loosening.14Hall D.J. Pourzal R. Jacobs J.J. What surgeons need to know about ALTR in THA.J Arthroplasty. 2020; 35: 555https://doi.org/10.1016/j.arth.2020.01.016Abstract Full Text Full Text PDF Scopus (12) Google Scholar,16Hussey D.K. McGrory B.J. Ten-year cross-sectional study of mechanically assisted crevice corrosion in 1352 consecutive patients with metal-on-polyethylene total hip arthroplasty.J Arthroplasty. 2017; 32: 2546https://doi.org/10.1016/j.arth.2017.03.020Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar In most cases, metallosis is confined to the joint capsule and periprosthetic tissues. However, rare cases of metal migration to the skin and skin discoloration have been reported.1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar,5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar, 32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar Systemic metal toxicity is also a possible complication of extensive metallosis.6Bradberry S.M. Wilkinson J.M. Ferner R.E. Systemic toxicity related to metal hip prostheses.Clin Toxicol. 2014; 52: 837-847https://doi.org/10.3109/15563650.2014.944977Crossref PubMed Scopus (143) Google Scholar Although uncommon, metallosis is not rare. It has been mostly reported after total hip arthroplasty, with an estimated risk of 1%-10%, accounting for three-quarters of all revision surgery.14Hall D.J. Pourzal R. Jacobs J.J. What surgeons need to know about ALTR in THA.J Arthroplasty. 2020; 35: 555https://doi.org/10.1016/j.arth.2020.01.016Abstract Full Text Full Text PDF Scopus (12) Google Scholar,16Hussey D.K. McGrory B.J. Ten-year cross-sectional study of mechanically assisted crevice corrosion in 1352 consecutive patients with metal-on-polyethylene total hip arthroplasty.J Arthroplasty. 2017; 32: 2546https://doi.org/10.1016/j.arth.2017.03.020Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar,17Jacobs J.J. Corrosion at the head-neck junction: why is this happening now?.J Arthroplasty. 2016; 31: 1378https://doi.org/10.1016/j.arth.2016.03.029Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar,24Murali R. Bonar F. Kirsh G. Walter W.K. Walter W.L. Osteolysis in third-generation alumina ceramic-on-ceramic hip bearings with severe impingement and titanium metallosis.J Arthroplasty. 2008; 23: 1240.e13-1240.e19https://doi.org/10.1016/j.arth.2007.10.020Abstract Full Text Full Text PDF Scopus (49) Google Scholar The majority of reported cases concern metal-on-metal prostheses, but all types of implants can be involved. In the majority of published cases, cobalt is the main metal responsible for metallosis and occasionally for metal intoxication. We report a case of metallosis with titanium skin discoloration after reverse total shoulder arthroplasty. After a road accident causing a comminuted right proximal humerus fracture, a 64-year-old woman was treated with a humeral prosthesis. However, 10 months later, in the context of persistent pain and severe disability due to implant failure, the humeral component was explanted and replaced by a reverse total shoulder arthroplasty (RTSA). At revision, there was no evidence of deep tissue metallosis around the joint and/or the humeral prosthesis. Shoulder pain and disability persisted after this second operation and became increasingly severe over the following months. After 6 to 9 months, bluish-grey discoloration was observed on and around the operative scar and on the anterior aspect of the right shoulder, and subsequently, on the anterior surface of the right arm and the elbow. The patient was referred to a dermatologist, who suspected allergic contact dermatitis, and performed patch-tests with chromium, cobalt, nickel, and methyl methacrylate, all of which gave negative results. Serial radiographs and computed tomography showed progressive loosening of the humeral component with humeral osteolysis. Three years after the accident, a third surgical procedure was performed for humeral reconstruction with tibial allograft and RTSA replacement. At revision, extensive blue-greyish pigmentation was observed, not only involving the skin but also the deep tissues around the joint and the humeral prosthesis. All pigmented deep tissues were resected, but no histologic or toxicologic examinations were performed, and examination of the explanted components was also not reported. Shoulder pain and disability were markedly improved after this last operation but did not resolve completely. Skin pigmentation, which was maximal before the third operation, neither progressed nor regressed. Two years later, the patient was referred to our toxicology unit to investigate possible metal poisoning from the previous prosthesis components. She presented with blue-greyish discoloration of the right elbow and anterior aspect of the right shoulder and arm (Fig. 1). She still complained of moderate right shoulder pain with limited range of motion, and clinical examination showed limitation of active elevation and rotation. Routine laboratory tests, including blood count, serum urea, and creatinine and liver function tests, yielded normal findings. As microalbuminuria, urine retinol-binding protein, and alpha-1-microglobulin were also in the normal ranges, there were no signs of glomerular or tubular renal impairment. The composition of the metallic components of the previous (second) shoulder prosthesis was investigated. The humeral insert, stem, spacer, cup, baseplate, and screws were made of titanium-based alloys with low concentrations of vanadium (3.5%-4.5%) and aluminum (5.5%-6.5%). The glenosphere was made of a cobalt-chromium alloy with low concentrations of molybdenum and nickel. Blood and urine samples were collected using collection systems suitable for trace metal ion analysis. Chromium and nickel were determined by Electrothermal Atomic Absorption Spectrometry (PinAAcle 900Z, Perkin Elmer), titanium and aluminum were determined by Inductively Coupled Optical Emission Spectrometry (iCAP 6300DV, Thermo Fisher Scientific), and cobalt, molybdenum, and vanadium were determined by Inductively Coupled Plasma-Mass Spectrometry (Elan DRCe, Perkin Elmer). The results of these determinations are presented in Table I. Serum titanium concentration was substantially elevated. Serum levels of all other metals were in the normal ranges, as were urine concentrations of all elements, including titanium.Table IResults of serum and urine metal analysis.LODLOQResultsReference value (RfV)Definition of the RfVUrine aluminum0.5 μg/L1.5 μg/L2.4 μg/L11.5 μg/LP95 of the distribution in a sample representative of the general population (Northern France, 2008-2010)26Nisse C. Tagne-Fotso R. Howsam M. Richeval C. Labat L. et al.Members of Health Examination Centres of the Nord − Pas-de-Calais region networkBlood and urinary levels of metals and metalloids in the general adult population of Northern France: The IMEPOGE study, 2008-2010.Int J Hyg Environ Health. 2017; 220: 341-363https://doi.org/10.1016/j.ijheh.2016.09.020Crossref PubMed Scopus (113) Google ScholarSerum chromium0.05 μg/L0.15 μg/L0.17 μg/L0.79 μg/LP95 of the distribution in volunteers from the general population (France, 2012)8Cesbron A. Saussereau E. Mahieu L. Couland L. Guerbet M. Goullé J.P. Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.J Anal Toxicol. 2013; 37: 401-405https://doi.org/10.1093/jat/bkt046Crossref PubMed Scopus (68) Google ScholarUrine chromium0.1 μg/L0.3 μg/L<LOQ0.65 μg/L0.54 μg/g creatinineP95 of the distribution in a sample representative of the general population (France, 2006-2007)11Fréry N. Fillol C. Garnier R. Falq G. Bidondo M.L. Guldner L. et al.Exposure of the French population to environmental chemicals. ENNS 2006-2007 study.Tox Anal Clin. 2017; 29: 441-482https://doi.org/10.1016/j.toxac.2017.06.002Crossref Scopus (8) Google ScholarSerum cobalt0.003 μg/L0.009 μg/L0.51 μg/L0.59 μg/LP95 of the distribution in volunteers from the general population (France, 2012)8Cesbron A. Saussereau E. Mahieu L. Couland L. Guerbet M. Goullé J.P. Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.J Anal Toxicol. 2013; 37: 401-405https://doi.org/10.1093/jat/bkt046Crossref PubMed Scopus (68) Google ScholarUrine cobalt0.003 μg/L0.009 μg/L0.47 μg/L0.85 μg/g creatinine1.40 μg/L1.13 μg/g creatinineP95 of the distribution in a sample representative of the general population (France, 2006-2007)11Fréry N. Fillol C. Garnier R. Falq G. Bidondo M.L. Guldner L. et al.Exposure of the French population to environmental chemicals. ENNS 2006-2007 study.Tox Anal Clin. 2017; 29: 441-482https://doi.org/10.1016/j.toxac.2017.06.002Crossref Scopus (8) Google ScholarSerum molybdenum0.05 μg/L0,17 μg/L0.75 μg/L1.15 μg/LP95 of the distribution in volunteers from the general population (France, 2012)8Cesbron A. Saussereau E. Mahieu L. Couland L. Guerbet M. Goullé J.P. Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.J Anal Toxicol. 2013; 37: 401-405https://doi.org/10.1093/jat/bkt046Crossref PubMed Scopus (68) Google ScholarUrine molybdenum0.15 μg/L0.30 μg/L18.7 μg/L34.0 μg/g creatinine137 μg/L123 μg/g creatinineP95 of the distribution in a sample representative of the general population (USA 2015-2016)25NhanesFourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, January 2019, Volume One. Centers for Disease Control and Prevention, Atlanta2019: 866https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Jan2019-508.pdfGoogle ScholarSerum nickel0.3 μg/L0.9 μg/L<LOQ1.26 μg/LP95 of the distribution in volunteers from the general population (France, 2012)8Cesbron A. Saussereau E. Mahieu L. Couland L. Guerbet M. Goullé J.P. Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.J Anal Toxicol. 2013; 37: 401-405https://doi.org/10.1093/jat/bkt046Crossref PubMed Scopus (68) Google ScholarUrine nickel0.3 μg/L0.9 μg/L2.7 μg/L4.9 μg/g creatinine4.54 μg/L3.77 μg/g creatinineP95 of the distribution in a sample representative of the general population (France, 2006-2007)11Fréry N. Fillol C. Garnier R. Falq G. Bidondo M.L. Guldner L. et al.Exposure of the French population to environmental chemicals. ENNS 2006-2007 study.Tox Anal Clin. 2017; 29: 441-482https://doi.org/10.1016/j.toxac.2017.06.002Crossref Scopus (8) Google ScholarSerum titanium0.5 μg/L1.5 μg/L40.8 μg/L2.56 μg/LP95 of the distribution in patients with well-functioning hip implants.35Swiatkowska I. Martin N.G. Henckel J. Apthorp H. Hamshere J. Hart A.J. Blood and plasma titanium levels associated with well-functioning hip implants.J Trace Elem Med Biol. 2020; 57: 9-17https://doi.org/10.1016/j.jtemb.2019.09.005Crossref PubMed Scopus (14) Google ScholarUrine titanium0.5 μg/L1.5 μg/L< LOQ<1 μg/L<1 μg/g creatinine60 to 80-year-old individuals with no metallic prostheses22Liu T.K. Liu S.H. Chang C.H. Yang R.S. Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty.Tokohu J Exp Med. 1998; 185: 253-262Crossref PubMed Scopus (39) Google ScholarUrine vanadium0.02 μg/L0.06 μg/L0.6 μg/L1.1 μg/g creatinine1.21 μg/L1.12 μg/g creatinineP95 of the distribution in a sample representative of the general population (Northern France, 2008-2010)26Nisse C. Tagne-Fotso R. Howsam M. Richeval C. Labat L. et al.Members of Health Examination Centres of the Nord − Pas-de-Calais region networkBlood and urinary levels of metals and metalloids in the general adult population of Northern France: The IMEPOGE study, 2008-2010.Int J Hyg Environ Health. 2017; 220: 341-363https://doi.org/10.1016/j.ijheh.2016.09.020Crossref PubMed Scopus (113) Google ScholarLOD, limit of detection; LOQ, limit of quantification; P95, 95th percentile.Bold = It is the only metal level above the corresponding reference value, in the table. Open table in a new tab LOD, limit of detection; LOQ, limit of quantification; P95, 95th percentile. Bold = It is the only metal level above the corresponding reference value, in the table. The patient refused skin biopsy but agreed to follow-up urine and serum metal assays 1 year after the first assessment. At this second evaluation, serum titanium was still elevated (33.9 μg/L). Serum and urine levels of all other elements were in the normal ranges. Urine titanium was not assayed. Shoulder, arm, and elbow pigmentation remained unchanged. Skin discoloration is a rare manifestation of metallosis complicating joint arthroplasty. To our knowledge, only 12 publications have reported a total of 13 cases of this type of local cutaneous metallosis.1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar, 4Babis G.C. Stavropoulos N.A. Sasalos G. Ochsenkuehn-Petrpoulou M. Megas P. Metallosis and elevated serum levels of tantalum following failed revision hip arthroplasty – a case report.Acta Orthopaed. 2014; 85: 677-680https://doi.org/10.3109/17453674.2014.950816Crossref PubMed Scopus (10) Google Scholar, 5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar, 32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar, 4Babis G.C. Stavropoulos N.A. Sasalos G. Ochsenkuehn-Petrpoulou M. Megas P. Metallosis and elevated serum levels of tantalum following failed revision hip arthroplasty – a case report.Acta Orthopaed. 2014; 85: 677-680https://doi.org/10.3109/17453674.2014.950816Crossref PubMed Scopus (10) Google Scholar, 5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar, 7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar, 20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar, 28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar, 31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar, 32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar, 37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar, 3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar, 4Babis G.C. Stavropoulos N.A. Sasalos G. Ochsenkuehn-Petrpoulou M. Megas P. Metallosis and elevated serum levels of tantalum following failed revision hip arthroplasty – a case report.Acta Orthopaed. 2014; 85: 677-680https://doi.org/10.3109/17453674.2014.950816Crossref PubMed Scopus (10) Google Scholar, 5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar, 6Bradberry S.M. Wilkinson J.M. Ferner R.E. Systemic toxicity related to metal hip prostheses.Clin Toxicol. 2014; 52: 837-847https://doi.org/10.3109/15563650.2014.944977Crossref PubMed Scopus (143) Google Scholar, 7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 8Cesbron A. Saussereau E. Mahieu L. Couland L. Guerbet M. Goullé J.P. Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.J Anal Toxicol. 2013; 37: 401-405https://doi.org/10.1093/jat/bkt046Crossref PubMed Scopus (68) Google Scholar, 9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar, 10Fabi D. Levine B. Majoras N. Chronic renal failure and catastrophic failure of an acetabular component.J Bone Joint Surg. 2011; 93: e68https://doi.org/10.2106/JBJS.J.01262Crossref PubMed Scopus (4) Google Scholar, 11Fréry N. Fillol C. Garnier R. Falq G. Bidondo M.L. Guldner L. et al.Exposure of the French population to environmental chemicals. ENNS 2006-2007 study.Tox Anal Clin. 2017; 29: 441-482https://doi.org/10.1016/j.toxac.2017.06.002Crossref Scopus (8) Google Scholar, 12Geraets L. Oomen A.G. Krystek P. Jacobsen N.R. Wallin H. Laurentie M. et al.Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats.Part Fibre Toxicol. 2014; 11: 30https://doi.org/10.1186/1743-8977-11-30Crossref PubMed Scopus (182) Google Scholar, 13Golasik M. Herman M. Olbert M. Librowski T. Szklaezewicz J. Piekoszewski W. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.Toxicol Lett. 2016; 247: 56-61https://doi.org/10.1016/j.toxlet.2016.02.009Crossref PubMed Scopus (13) Google Scholar,23Mayo Clinic Laboratories. Titanium, serum. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/89367. Accessed December 21, 2021.Google Scholar In one case, light blue discoloration was observed following hip arthroplasty with metallic components composed of either tantalum or a titanium-aluminum vanadium alloy.4Babis G.C. Stavropoulos N.A. Sasalos G. Ochsenkuehn-Petrpoulou M. Megas P. Metallosis and elevated serum levels of tantalum following failed revision hip arthroplasty – a case report.Acta Orthopaed. 2014; 85: 677-680https://doi.org/10.3109/17453674.2014.950816Crossref PubMed Scopus (10) Google Scholar This skin pigmentation was associated with clinical and radiological signs of prosthesis failure. Revision surgery revealed extensive metallosis of the tissues surrounding the acetabular component, and X-ray fluorescence analysis showed that the main metallic component responsible for this metallosis was tantalum; serum tantalum level was also dramatically elevated. In the other 12 published cases, the skin discoloration was similar to that observed in our case, bluish-grey to bluish-black1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar,5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar, 32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar and occurred after hip,1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar knee,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar elbow,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar or, as in our case, shoulder20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar arthroplasty. In most cases, skin discoloration was associated with clinical and sometimes radiologic signs of prosthesis failure. When joint revision surgery was performed, it always showed, as in our case, extensive metallosis of deep tissues surrounding one or several of the metallic prosthetic components, with bluish-black discoloration.5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,20Jayasekera N. Gouk C. Patel A. Eyres K. Apparent skin discoloration about the knee joint: a rare sequelae of metallosis after total knee replacement.Case Rep Orthop. 2015; 2015: 891904https://doi.org/10.1155/2015/891904Crossref PubMed Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar, 32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 33Sporer S.M. Chalmers P.N. Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty after acetabular liner dissociation.J Arthroplasty. 2012; 27: 1580.e13-1580.e16https://doi.org/10.1016/j.arth.2012.01.008Abstract Full Text Full Text PDF Scopus (8) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar When the compositions of the alloys constituting the prosthesis components were indicated in the case report, they always consisted of titanium-based alloys, sometimes together with cobalt-chromium alloys.1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar,32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar When performed, histologic examination of the skin and/or tissues surrounding the prostheses showed black granules both outside the cells and inside macrophages, histiocytes, and sometimes multinuclear giant cells, together with moderate inflammatory infiltrate.1Akimoto M. Hara H. Suzuki H. Metallosis of the skin mimicking malignant skin tumour.Br J Dermatol. 2003; 149: 653https://doi.org/10.1046/j.1365-2133.2003.05387.xCrossref PubMed Scopus (23) Google Scholar,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar,5Berber O. Pearse E.O. Tennet T.D. Metallosis and cutaneous metal pigmentation in a reverse shoulder replacement.Shoulder & Elbow. 2013; 5: 195-197https://doi.org/10.1111/sae.12012Crossref Scopus (4) Google Scholar,7Callender V.D. Cardwell L.A. Munhutu M.N. Bigby U. Rodney I.J. Cutaneous metallosis in patient with knee prosthesis composed of cobalt-chromium molybdenum alloy and titanium-aluminum-vanadium alloy.JAAD Case Rep. 2015; 1: 36-37https://doi.org/10.1016/j.jdcr.2014.10.009Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar,28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar,32Sochol K.M. Charen D.A. Andelman S.M. Parsons B.O. Cutaneous metallosis following reverse total shoulder arthroplasty.J Shoulder Elbow Surg. 2018; 27: e230-e233https://doi.org/10.1016/j.jse.2018.02.074Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,37Willis-Owen C.A. Keene G.C. Oakeshott R.D. Early metallosis-related failure after total Knee replacement.J Bone Joint Surg. 2011; 93B: 205-209https://doi.org/10.1302/0301-620X.93B2.25150Crossref Scopus (32) Google Scholar Chemical characterization of the pigmented granules was performed in only 3 cases and showed that the main elemental component was titanium in 2 cases.28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar,31Seong S.C. Le M.C. Moon Y.W. Lee J.C. Failed TKA with titanium-induced tissue response.Korean J Orthop. 1996; 31: 720-729Crossref Google Scholar In the third case,3Asahina A. Fujita H. Fukuda S. Kai H. Yamamoto M. Hattori N. et al.Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not?.Br J Dermatol. 2007; 157: 1074-1076https://doi.org/10.1111/j.1365-2133.2007.08161.xCrossref PubMed Scopus (9) Google Scholar an analytical error is highly probable, as the main components of metallic granules were identified to be iron and copper, although the metallic prosthetic components were made of a titanium alloy or cobalt-chromium alloy. The previously published case reports of skin discoloration associated with metallic joint prostheses did not include any blood or urine metal assays. In our case, all metals present in the composition of the prosthetic components were assayed in serum and/or urine. All concentrations were situated within the normal ranges, except for serum titanium, which was substantially elevated when measured for the first time, 5 years after the onset of skin discoloration, and 2 years after the last revision surgery that had improved shoulder function and stabilized skin discoloration (Table I). Serum titanium was in the same range when assayed 1 year later. Urine titanium level was normal (Table I), which is not surprising, as renal excretion of titanium is known to be very slow,12Geraets L. Oomen A.G. Krystek P. Jacobsen N.R. Wallin H. Laurentie M. et al.Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats.Part Fibre Toxicol. 2014; 11: 30https://doi.org/10.1186/1743-8977-11-30Crossref PubMed Scopus (182) Google Scholar,15Heringa M.B. Geraets L. van Eijkeren J.C.H. Vandebriel R.J. de Jong W.H. Oomen A.G. Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations.Nanotoxicology. 2016; 10: 1515-1525https://doi.org/10.1080/17435390.2016.1238113Crossref PubMed Scopus (93) Google Scholar and several publications have shown that metal concentrations may be elevated in the blood (whole blood, plasma, or serum),18Jacobs J.J. Silverton G. Hallab N.J. Skipor A.K. Patterson L. Black J. et al.Metal release and excretion from cementless titanium alloy total knee replacements.Clin Orthop Relat Res. 1999; 358: 173-180Crossref PubMed Google Scholar,19Jacobs J.J. Skipor A.K. Patterson L.M. Hallab N.J. Paprosky W.G. Black J. et al.Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study.J Bone Joint Surg. 1998; 80A: 1447-1458Crossref Google Scholar,22Liu T.K. Liu S.H. Chang C.H. Yang R.S. Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty.Tokohu J Exp Med. 1998; 185: 253-262Crossref PubMed Scopus (39) Google Scholar,27Nuevo-Ordonez Y. Montes-Bayon M. Blanco-Gonzalez E. Paz-Aparicio J. Raimundez J.D. Tejerina J.M. et al.Titanium release in serum of patients with different bone fixation implants and its interaction with serum biomolecules at physiological levels.Ann Bioanal Chem. 2011; 401: 2747-2754https://doi.org/10.1007/s00216-011-5232-8Crossref PubMed Scopus (63) Google Scholar,29Reiner T. Bader N. Panzram B. Bülhoff M. Omlor G. Kretzer J.P. et al.In vivo blood metal ion levels in patients after total shoulder arthroplasty.J Shoulder Elbow Surg. 2019; 28: 539-546https://doi.org/10.1016/j.jse.2018.08.027Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,30Sarmiento-Gonzalez A. Marchante-Gayon J.M. Terejina-Lobo J.M. Paz-Jimenez J. Sanz-Medel A. High-resolution ICP-MS determination of Ti, V, Cr , Co, Ni and Mo in human blood and urine of patients implanted with a hip or knee prosthesis.Anal Bioanal Chem. 2008; 391: 2583-2589https://doi.org/10.1007/s00216-008-2188-4Crossref PubMed Scopus (74) Google Scholar but not in urine18Jacobs J.J. Silverton G. Hallab N.J. Skipor A.K. Patterson L. Black J. et al.Metal release and excretion from cementless titanium alloy total knee replacements.Clin Orthop Relat Res. 1999; 358: 173-180Crossref PubMed Google Scholar,22Liu T.K. Liu S.H. Chang C.H. Yang R.S. Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty.Tokohu J Exp Med. 1998; 185: 253-262Crossref PubMed Scopus (39) Google Scholar in patients with titanium alloy prostheses. Patients with loosened titanium components generally exhibit elevated blood titanium levels (up to 620 μg/L for serum or plasma).2Alexander-Malahias M. de Martino I. Gu A. Baral E. Wright T.M. Sculco P.K. Complete wear-through of a metal backed acetabular cup in an ambulatory patient.Arthroplasty Today. 2019; 5: 394-400https://doi.org/10.1016/j.artd.2019.09.008Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar,10Fabi D. Levine B. Majoras N. Chronic renal failure and catastrophic failure of an acetabular component.J Bone Joint Surg. 2011; 93: e68https://doi.org/10.2106/JBJS.J.01262Crossref PubMed Scopus (4) Google Scholar,34Swiatkowska I. Martin N. Hart A.J. Blood titanium level as a biomarker of orthopaedic implant wear.J Trace Elem Med Biol. 2019; 53: 120-128https://doi.org/10.1016/j.jtemb.2019.02.013Crossref PubMed Scopus (24) Google Scholar,36Tarpada S.P. Loloi J. Schwechter E.M. A case of titanium pseudotumor and systemic toxicity after total hip arthroplasty polyethylene failure.Arthroplasty Today. 2020; 6: 710-715https://doi.org/10.1016/j.artd.2020.07.033Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Blood titanium level can be considered to be a biomarker of orthopedic implant wear. The current Mayo clinic laboratory guidelines indicate that a serum titanium concentration > 10 μg/L suggests prosthesis wear.23Mayo Clinic Laboratories. Titanium, serum. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/89367. Accessed December 21, 2021.Google Scholar However, this recommended cutoff value is based on the studies by Liu et al,22Liu T.K. Liu S.H. Chang C.H. Yang R.S. Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty.Tokohu J Exp Med. 1998; 185: 253-262Crossref PubMed Scopus (39) Google Scholar and Jacobs et al,19Jacobs J.J. Skipor A.K. Patterson L.M. Hallab N.J. Paprosky W.G. Black J. et al.Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study.J Bone Joint Surg. 1998; 80A: 1447-1458Crossref Google Scholar both published in 1998, and using analytical methods and instruments with quantification limits that are now considered not to be sufficiently low. In a recent work, based on a series of 95 patients with well-functioning hip implants, with a mean follow-up of 8.5 years, the 95th percentile of the distribution of plasma titanium level was 2.56 μg/L and 2.20 μg/L for whole-blood titanium level. The authors proposed these 2 values as laboratory reference levels in patients with well-functioning titanium implants.34Swiatkowska I. Martin N. Hart A.J. Blood titanium level as a biomarker of orthopaedic implant wear.J Trace Elem Med Biol. 2019; 53: 120-128https://doi.org/10.1016/j.jtemb.2019.02.013Crossref PubMed Scopus (24) Google Scholar In only 2 published cases, possible signs of systemic toxicity were associated with titanium metallosis following arthroplasty failure. In the first case, a 57-year-old woman with failure of her hip arthroplasty and massive titanium metallosis also complained of weakness, headaches, and unspecified visual disorders. Plasma titanium level was 460 μg/L, and plasma cobalt, chromium, and aluminum levels were in the normal ranges. The case report did not describe any further investigations, and the clinical course after surgical revision is unknown.36Tarpada S.P. Loloi J. Schwechter E.M. A case of titanium pseudotumor and systemic toxicity after total hip arthroplasty polyethylene failure.Arthroplasty Today. 2020; 6: 710-715https://doi.org/10.1016/j.artd.2020.07.033Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In the second case, a 64-year-old male patient with arterial hypertension was also found to have renal failure (serum creatinine: 2.26 μg/dL) at the time of discovery of the failure of his hip arthroplasty. At the time of the surgical revision, he presented massive titanium metallosis with high serum titanium (457 μg/L) and only moderately elevated serum cobalt (1.6 μg/L), chromium (0.9 μg/L), and nickel (0.5 μg/L) levels. Six months after revision, serum titanium and serum creatinine levels had both decreased to 150 μg/L and 1.6 mg/dL, respectively.10Fabi D. Levine B. Majoras N. Chronic renal failure and catastrophic failure of an acetabular component.J Bone Joint Surg. 2011; 93: e68https://doi.org/10.2106/JBJS.J.01262Crossref PubMed Scopus (4) Google Scholar Experimentally, the ionic form of titanium mainly accumulates in the kidneys,13Golasik M. Herman M. Olbert M. Librowski T. Szklaezewicz J. Piekoszewski W. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.Toxicol Lett. 2016; 247: 56-61https://doi.org/10.1016/j.toxlet.2016.02.009Crossref PubMed Scopus (13) Google Scholar which are also the main target organs for toxic effects.21Jin T. Berlin M. Titanium.in: Nordberg G.F. Fowler B.A. Nordberg M. Friberg L.T. Handbook on the toxicology of metals. 3rd ed. 9780123694133 Academic Press, New-York2007: 861-870Crossref Scopus (7) Google Scholar No sign of systemic effects was present in our case, but serum titanium levels were much lower. In our case, skin pigmentation appeared 6 to 9 months after RTSA, then progressively extended for 3 years until arthroplasty revision with resection of pigmented deep tissues. Skin discoloration subsequently remained unchanged for the next 3 years. The clinical course of skin pigmentation after arthroplasty revision has been described in only 2 previously published cases: in the first case, discoloration of the left hip remained unchanged during the 14-year follow-up of a well-functioning revision total hip arthroplasty9Creighton-Smith M. McGrory B.J. Tolocica I. Long-term tattooing as a manifestation of metallosis in acetabular liner wear-through: a report of two cases.Curr Orthop Pract. 2015; 26: 64-67https://doi.org/10.1097/BCO.0000000000000189Crossref Scopus (4) Google Scholar; in the second case, metallic discoloration of the right shin progressively faded and disappeared within 4 years, after revision of a right knee arthroplasty.28Park J.Y. Shin D.H. Choi J.S. Kim K.H. Metallic discoloration of the right shin caused by titanium alloy prostheses in a patient with right total knee replacement.Ann Dermatol. 2013; 25: 356-359https://doi.org/10.5021/ad.2013.25.3.356Crossref PubMed Scopus (9) Google Scholar Greyish-blue skin discoloration of scars and/or para-articular areas is a rare manifestation of titanium alloy prosthesis failure. It is always associated with extensive deep tissue metallosis, whereas most cases of metallosis after arthroplasty do not include skin pigmentation. The presence of skin pigmentation always indicates the need for revision and warrants assessment of systemic diffusion of metals by assaying blood titanium, as well as blood cobalt and chromium levels, as titanium alloy components of articular prostheses are generally associated with cobalt/chromium alloy components.