Endovascular Treatment of Cerebrovascular Lesions Using Nickel- or Nitinol-Containing Devices in Patients with Nickel Allergies

DISCUSSION

Cases of cutaneous allergic reactions to metallic orthopedic and surgical implants are well documented.^17,18 However, the evidence that endovascularly placed intravascular devices can induce a deleterious allergic response is more debatable. Although studies in the cardiology literature have associated nickel allergies with an increased incidence of in-stent stenosis,^8,9,13 prospective studies have not confirmed this relationship.^10⇓-12 Nonetheless, neuroendovascular surgeons and interventionalists may be wise to be concerned about placing nickel-containing devices in patients who have reported nickel or other metal allergies.¹⁹ Despite the overall prevalence of nickel allergies within the general population (10%–15%)^1,2 and the increased use of nickel-containing devices for the treatment of cerebrovascular lesions, relatively few studies have been published on the subject.

Tonetti et al⁵ reported the successful treatment with a nickel-containing flow-diverting stent of 2 patients who had cutaneous nickel allergies; neither patient demonstrated any allergic reactions or in-stent stenosis at prolonged follow-up. As in our series of 7 patients, neither of their 2 patients had received periprocedural prophylactic treatment with steroids or antihistamines. Similarly, Wallace et al⁷ reported that, in a series of 20 patients with metal allergies who underwent cerebral aneurysm treatment with nickel-containing flow-diverting stents, there were no apparent allergic reactions despite the lack of periprocedural prophylactic treatment with steroids or antihistamines. Our series further supports these results, because we found no evidence of allergic or other adverse clinical reactions among our patients. Moreover, we found that, in all 6 patients with angiographic follow-up, complete obliteration of the vascular lesion was demonstrated without adverse sequelae.

Although our results suggest that neuroendovascular treatment with nickel-containing devices may be safe in patients with nickel or other metal allergies, other authors have reported some cases of adverse effects possibly attributable to allergic reactions to metal. Fujii et al¹⁴ reported a case of delayed in-stent stenosis in a patient with a cobalt allergy who was treated with a nickel-containing flow-diverting stent. Other authors have reported cases of diffuse cerebral edema with seizures or focal neurologic deficits after placement of a nickel-containing device.^13,15 However, the exact etiology in these cases has not been fully elucidated. Fortunately, the patients in these cases were successfully treated with systemic steroids, which resulted in radiologic and clinical resolution of their symptoms.^13,15 Similarly, other authors have reported radiographic sequelae, including foci of MR imaging enhancement in the catheterized territory that developed in the weeks after the procedure and responded to steroid treatment.^16,20,21 Together, these findings suggest that a delayed, steroid-responsive hypersensitvity-like reaction is possible after endovascular treatment; however, the exact etiology remains to be fully elucidated. On the basis of our results and those of other authors, we believe that there is a low relative risk of severe allergic reactions after treatment with nickel-containing neuroendovascular devices.

However, precautionary steps to help mitigate any potential risk should be considered. We did not pursue nickel allergy patch testing for the patients in our series who reported having a nickel allergy before their treatment with a nickel-containing device; however, performing a patch test before an elective treatment may be a reasonable approach. Other authors recommend this strategy to enable better patient counseling and to provide an opportunity to consider treatment alternatives.²² However, others have reported that patch testing was of very limited clinical utility for patients undergoing endovascular treatment.¹¹ The incidence of nickel hypersensitivities is likely underreported in retrospective studies. To better address this area of concern and to assist in future analyses and patient counseling, we have implemented a policy of explicitly asking all patients about any potential metal allergies or hypersensitivities when they are scheduled to undergo an elective endovascular treatment in which a nickel-containing device is part of the treatment plan.

One potential reason for the lack of frequent consequential adverse reactions after placement of nickel-containing cerebrovascular stents in patients with reported nickel allergies is that the commonly used neurovascular stents do not actually release nickel ions. The release of nickel ions is necessary to induce a nickel hypersensitivity response via immune cell activation. Recent in vitro work by Vanent et al²³ determined that commonly used nickel-containing cerebrovascular stents—including those used in our series—do not actually release nickel ions. These findings correlate with our clinical results because the lack of free nickel ion release from the stents would preclude a clinical hypersensitivity response. Taken together, these results suggest that patients with a nickel allergy who require endovascular treatment for cerebrovascular lesions may be safely treated with nickel-containing stents. This conclusion is supported by the general observation that the percentage of patients with adverse effects after treatment with nickel-containing devices (generally reported as markedly <10%^24⇓⇓-27) is notably less than the estimated prevalence of nickel allergy or hypersensitivity within the general population (10%–15%).²⁸ However, neither our results nor the previously reported data preclude a causal relationship between a metal or nickel allergy and any adverse reaction. Therefore, to more comprehensively address the relative risk and possible causation, larger prospective databases are required that systematically document allergy status and identify potential clinical and imaging sequelae.

Our study was limited by its retrospective nature and the small patient cohort. Limitations included a lack of rigid standardization of clinical and radiologic follow-up timing, technique, and granularity. These limitations may have obscured minor clinical or radiologic sequelae. Furthermore, we ascertained the presence of a cutaneous metal allergy from a retrospective chart review rather than from formal dermatologic allergy testing. Although we review allergies for all patients as part of our standard inpatient and clinic history and physical, it is possible that the sensitivity and specificity of this methodology produce both false-positive and false-negative results. It is important to note that, in light of population statistics, the number of patients with reported nickel or other metal allergies or hypersensitivities in our study likely underestimates the actual number of patients with such hypersensitivities. Future prospective studies are warranted that are designed to describe the safety and efficacy of nickel-containing devices in neurosurgery, the potential role of patch testing for nickel allergies, and the possible benefit of prophylactic treatment.