Hypersensitivity to implantable devices, albeit rare, is a growing problem. according to a report on biological responses to metal implants released by the Food and Drug Administration in September 2019. Large controlled studies are lacking, and the FDA has initiated extensive postmarketing reviews of certain metal implants in response to safety concerns. Further research is needed on the composition of these implants, the diverse spectrum of metals used, the physical environment in which they are implanted, and the immune response associated with implants.
Dr. Lily Talakoub
Local and systemic type IV hypersensitivity reactions can result from exposure to metal ions, which are thought to act as haptens and bind to proteins. The hapten-protein complex acts as the antigen for the T cell. Additionally, both acute and chronic inflammatory responses secondary to wound healing and foreign body reactions can occur. Neutrophils and macrophages elicit a tissue response, which can cause aseptic infection, loosening of joints, and tissue damage. Furthermore, corrosion of metal implants can lead to release of metal ions, which can have genotoxic and carcinogenic effects.
Clinical and subclinical effects of implantable devices depend on the device itself, the composition of the device, the tissue type, and an individual’s immune characteristics. Metal debris released from implants can activate innate and adaptive immune responses through a variety of different mechanisms, depending on the implant type and in what tissues the implant is placed. In the case of orthopedic implants, the most common implants, osteoclasts can sense metal and induce proinflammatory cytokines, which can result in corrosion and uptake of metal particles. Metal devices used in the central nervous system, such as intracerebral electrodes, can cause inflammatory responses leading to tissue encapsulation of electrodes. Corrosion of electrodes and release of metal ions can also impede ion channels in the CNS, blocking critical neuron-signaling pathways. Inflammatory reactions surrounding cardiac and vascular implants containing metal activate coagulation cascades, resulting in endothelial injury and activation of thrombi.
Despite the commonly used term “metal allergy” that delineates a type IV hypersensitivity reaction, reports in the literature supports the existence of both innate and adaptive immune responses to metal implanted in tissues. The recommended terminology is “adverse reactions to metal debris.” The clinical presentation may not be straightforward or easily attributed to the implant. Diagnostic tools are limited and may not detect a causal relationship.
Dr. Naissan O. Wesley
Clinical symptoms can range from local rashes and pruritus to cardiac damage, depression, vertigo, and neurologic symptoms; autoimmune/autoinflammatory reactions including chronic fatigue and autoimmune-like systemic symptoms, such as joint pain, headaches, and hair loss, have also been reported in association with implants containing metal. In addition to pruritus, dermatologic manifestations can include erythema, edema, papules, vesicles, as well as systemic hypersensitivity reactions. Typically, cutaneous reactions usually present within 2 days to 24 months of implantation and may be considered surgical-site infections. Although these reactions can be treated with topical or oral corticosteroids, removal of the device is frequently needed for complete clearance.
In clinical practice, it has been frustrating that potential adverse reactions to metal implants are often overlooked because they are thought to be so rare. There are case series documenting metal implant hypersensitivity, but the actual prevalence of hypersensitivity or autoinflammatory reactions is not known. Testing methods are often inaccurate; therefore, identification of at-risk individuals and management of symptomatic patients with implants is important.
The 2016 American Contact Dermatitis Society guidelines do not recommend preimplantation patch testing unless there is a suspected metal allergy. However, patch testing cannot identify the extent of corrosion, autoinflammatory reactions, and foreign body reactions that can occur.
We must keep an open mind in patients who have implanted devices and have unusual or otherwise undefined symptoms. Often, the symptoms do not directly correspond to the site of implantation and the only way to discern whether the implant is the cause and to treat symptoms is removal of the implanted device.
Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at dermnews@mdedge.com. They had no relevant disclosures.
References
Food and Drug Administration. Biological Responses to Metal Implants. 2019 Sep. https://www.fda.gov/media/131150/download.
Atwater AR, Reeder M. Cutis. 2020 Feb;105(2):68-70.
Schalock PC et al. Dermatitis. Sep-Oct 2016;27(5):241-7.