Allergic Reaction to Vanadium Causes a Diffuse Eczematous Eruption and Titanium Alloy Orthopedic Implant Failure

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21