title: Hypersensitivity reactions to metal implants: laboratory options.
abstract: All implant compounds undergo an electrochemical process when in contact with biological fluids, as well as mechanical corrosion due to abrasive wear, with production of metal debris that may inhibit repair processes. None of the commonly-used methods can diagnose implant allergies when used singly, therefore a panel of tests should be performed on allergic patients as pre-operative screening, or when a postoperative metal sensitisation is suspected.
  
  
  
  We analysed patients with painful prostheses and subjects prone to allergies using the Patch Test in comparison with the Lymphocyte Transformation Test. Cytokine production was evaluated to identify prognostic markers for early diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal rearrangement was visualised by confocal microscopy.
  
  
  
  Our results demonstrate that the Lymphocyte Transformation Test can identify patients who have a predisposition to develop allergic reactions and can confirm the diagnosis of hypersensitivity in patients with painful prostheses. The prevalence of a Th2-cytokine pattern may be used to identify predisposition to the development of allergic diseases, while the selective presence of osteoclastogenic cytokines may be used as predictor of a negative outcome in patients with painful prosthesis. The hypothesis of the prognostic value of these cytokines as early markers of aseptic loosening is attractive, but its confirmation would require extensive testing.
  
  
  
  The Lymphocyte Transformation Test is the most suitable method for testing systemic allergies. We suggest that the combined use of the Patch Test and the Lymphocyte Transformation Test, associated with cytokine detection in selected patients, could provide a useful tool for preventive evaluation of immune reactivity in patients undergoing primary joint replacement surgery, and for clinical monitoring of the possible onset of a metal sensitization in patients with implanted devices.
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Carossino
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Carulli
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ciuffi
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carossino
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Giorgia Donata
authors.initials: GD
authors.lastname: Zappoli Thyrion
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zonefrati
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Innocenti
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy. marialuisa.brandi@unifi.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects* / Q000295:instrumentation; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D003599:Cytoskeleton / Q000648:ultrastructure; D004705:Endocytosis; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008213:Lymphocyte Activation; D008297:Male; D008670:Metals / Q000009:adverse effects*; D018613:Microscopy, Confocal; D010146:Pain / Q000209:etiology; D010147:Pain Measurement; D010328:Patch Tests; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D019736:Prostheses and Implants / Q000009:adverse effects*; D011475:Prosthesis Failure; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008670:Metals
keywords: Cytokines; Knee arthroplasty; Lymphocyte transformation test; Metal sensitivity; Patch test