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

Abstract 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.