I`ll Bet You a Nickel You Don`t Ask

My wife is allergic to nickel. Cheap jewelry gives her a rash. I know this because early in our relationship I was told that any gift of jewelry had to be at least 14 karat gold. So-called white gold is problematic as it contains either nickel or palladium, but seems to be okay if it meets karat criteria. But nickel is also widely used in medical devices (the “NI” in nitinol refers to its nickel content and nickel is also present in stainless steel). Would there be a problem if my wife needed transcatheter closure of an atrial septal defect (ASD), or a coronary stent?

Part of the answer is in this issue of the Journal of Invasive Cardiology, where Verma et al¹ report on differences in the nickel elution properties of ASD closure devices as well as sternal wires used after thoracotomy. The teaching points of their report are:

1. Their study supports earlier reports of nickel release after deployment of ASD closure devices.²
2. After deployment, serum levels of nickel rise, possibly until endothelialization is complete.
3. At 24 hours, the Amplatzer atrial septal occluder device and sternal wires had more nickel elution than the other devices, but at 90 days, the atrial septal occluder was the only device that still eluted significant amounts of nickel. 

These are not unexpected findings, but why are issues with nickel elution after ASD closure not more common? It is estimated that almost 20% of women and 3% of men are allergic to nickel.³ Thus, it is reasonable to conclude that in nickel-sensitive patients, such high levels of nickel after ASD occlusion might result in clinical symptoms. Indeed, Rigatelli et al have reported a clinical syndrome of chest pain, leukocytosis, and dyspnea in nickel-sensitive patients.⁴ Although the number of patients in their study is small, their findings cannot be disregarded. Nor can we ignore a 2011 report by Swamendra et al that detailed explantation of ASD closure devices. In that report, less than one-half of the surgical explantations were due to chest pain (thought to be due to nickel sensitivity). Other causes were residual shunts, thrombus on the device, pericardial effusion, perforation, recurrent stroke, endocarditis, and “undocumented.”⁵  

In another report, Wertman et al studied ASD devices, nickel allergy, and migraine headaches.⁶ Their patients received nickel allergy patch testing with the TRUE skin test, but patch testing was available in only 37 patients. There were 7 patients (5%) who noted new-onset migraine headaches or increased frequency and severity of headaches or aura post procedure. The numbers are small, and new-onset migraine may not be enough to cause a major concern after ASD closure (though I am sure anyone with migraines will disagree). 

Unfortunately, none of the studies, with the possible exception of Rigatelli, answers the question about my wife in the first paragraph. There clearly appears to be nickel release in closure devices that contain relatively larger amounts of nickel. But the relation of skin testing to outcomes, the presence (by history) of nickel sensitivity, and the actual incidence of clinical complications seems unclear. The issue is further complicated by the fact that coronary stents, orthopedic devices (think hip replacement), and other implantable devices often contain nickel.  

Returning to the ASD occluder question, it seems to me that in the absence of clearer data, prudence should dictate clinical decisions. If a patient is about to undergo ASD closure, we should routinely ask if they have a nickel allergy. If the answer is “yes,” perhaps skin testing should be the next step. However, that demands a consultation/referral, delay in closure, and greater expense. Even after the results are in, they do not support a specific clinical strategy. Not all skin-test positive patients will have symptoms after ASD closure that are nickel sensitivity related. Also, if nickel allergy is so common, we should see a lot more patients with symptoms after closure. Nonetheless, if skin testing is positive, closure with a device containing less nickel (or surgical closure) should be considered. For now, it boils down to making the best clinical decision with limited data. There is no doubt we need more studies concerning nickel sensitivity and clinical outcomes for a host of interventions. But I doubt that large randomized studies will ever be done. Device companies are not likely to support expensive trials to perhaps prove their products are unsafe. For now, the consensus seems to be best summarized by Morton J. Kern in a short poll of interventional cardiologists in the United States. He asked a group of his colleagues three questions.⁷ (1) Do you test for nickel allergy? (2) Do you treat for nickel allergy? If yes, with what, and why? (3) Do you pick stents based on fear of allergy?

For coronary stenting, the answer was a triple “no.” But for atrial septal defect/patent foramen ovale closure, the answers were mixed. Do you ask, and does the answer change your strategy?

References

1. Verma DR, Khan MF, Tandar A, et al. Nickel elution properties of contemporary interatrial shunt closure devices. J Invasive Cardiol. 2015;27(2):99-104. 
2. Reis MW, Kampmann C, Rupprecht HJ, Hintereder G, Hafner G, Meyer J. Nickel release after implantation of the Amplatzer occluder. Am Heart J. 2003;145(4):737-741.
3. Thyssen JP, Mennie T. Metal allergy — a review on exposures, penetration, genetics, prevalence, and clinical implications. Chem Res Toxicol. 2010;23(2):309-318.
4. Rigatelli G, Cardioli P, Giordan M, et al. Nickel allergy in interatrial shunt device-based closure patients. Congenit Heart Dis. 2007;2(6):416-420.
5. Verma SK,  Tobis JM. Explantation of atrial septal closure devices. A multicenter survey. JACC Cardiovasc Interv. 2011;4(5):579-585.
6. Wertman B, Azarbal B, Riedl M, Tobis J. Adverse events associated with nickel allergy in patients undergoing percutaneous atrial septal defect or patent foramen ovale closure. J Am Coll Cardiol. 2006;47(6):1226-1227.
7. Kern M. How should we manage nickel allergy in patients needing coronary stents? Cath Lab Digest. 2011;19(1).

From Emory University Hospital, Atlanta, Georgia.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no conflicts of interest regarding the content herein.

Address for correspondence: Peter C. Block, MD, Emory University Hospital

1364 Clifton Rd, Atlanta, GA 30322. Email: pblock@emory.edu