Titanium allergy to a hip implant presenting with a generalised rash and keratoderma

A 58-year-old male fractured his right hip at work, which required replacement with an uncemented Accolade 2 hip containing titanium, zirconium, molybdenum and iron, coated with a 'pure fix' hydroxyapatite. His immediate post-operative period in hospital was uneventful. He had a history of mild childhood flexural atopic dermatitis but no other skin conditions. He had no past history of metal exposure apart from a dental crown greater than 20 years ago. Some 10–12 weeks later, he developed a generalised rash on his legs and forearms, which later spread to his torso and hands. The rash continued to fluctuate over the following 6 months, with areas of annular erythema and also marked keratoderma involving his palms and soles. He responded to oral prednisolone and topical betamethasone dipropionate initially. He then developed erythroderma and required hospital admission for wet wraps with a short course of oral prednisolone. In view of the marked keratoderma, acitretin was trialled up to 50 mg/day with minimal response. He then required intermittent prednisolone and multiple courses of cephalexin because of recurrent staphylococcal skin infections. Dupilumab was trialled after 7 months but had to be ceased after 1 month because of worsening itch. Some 13 months after the hip replacement, the patient reported that pain was progressively increasing with movement. Repeated skin biopsies of the rash showed spongiotic dermatitis with compact parakeratosis. Patch testing was performed to our metal series on several occasions as reactions were difficult to interpret but it was concluded that he developed positive reactions on day 2 (+) and 4 (+) to titanium (IV) oxalate hydrate (5.0 pet). The patient was diagnosed with allergic contact dermatitis to titanium (Ti), which was present in his uncemented Accolade 2 hip. A hip revision was performed 16 months after the initial replacement with a polyethylene cup and a stainless-steel stem-head combination. It was noted intra-operatively that there were no macroscopic signs of granulation tissue, metallosis or loosening. The keratoderma and associated pruritus had reduced dramatically within 1 week of the revision, which allowed him to return to his hobbies. At review 6 weeks post-operation, he reported marked improvement in his pain levels and his generalised dermatitis had completely resolved on no medication. Signs and symptoms related to Ti allergy from implanted metal are varied and can include delayed wound healing,1 pain,2 instability and a localised rash.3 These can also be present in prosthetic joint failure unrelated to Ti allergy. Dear et al. described a patient with a localised pruritic plaque overlying a left anterior knee arthroplasty which had developed 4–6 weeks following the procedure.4 A localised rash overlying the area of the metal implant appears to be the most common cutaneous sign of allergy to an implant.4-7 Phedy et al. described the onset of a generalised rash 1 week post Ti implant, which completely resolved post implant removal.8 Shi et al. described a patch test positive Ti reaction with congestion to the eye and a pruritic leg rash 1 month after cervical fusion with a Ti implant (Zero-P device).9 However, in this case, our patient's rash was not only generalised in nature, without obvious accentuation over the hip area, but was also associated with marked keratoderma. Patch testing of Ti can be unreliable at times, because of low epidermal penetration of commercially available Ti salts, thus results can be difficult to interpret.10 To date, there are no certified guidelines on which titanium hapten(s) to test with. Establishing clear guidelines in the future would help alleviate some of the difficulties associated with titanium patch test interpretation. It has also been noted that Ti advertised as 'commercially pure' has been found to contain other metals such as nickel, which could be clinically relevant.11 In summary, Ti allergy presenting without a definite rash over the site of the implant can cause clinical uncertainty. This case involved much discussion between multiple specialists, detailed exploration of alternative diagnoses and shared decision making with the patient regarding surgical revision. Fortunately, there was a good outcome with resolution of the rash. James Fuller: Writing – original draft; writing – review and editing. Georgia Frost: Conceptualization. Hamish Gray: Conceptualization. Claire Ronaldson: Writing – original draft. Rosemary Nixon: Conceptualization; writing – review and editing. The authors declare no conflicts of interest.