How Should We Manage Nickel Allergy in Patients Needing Coronary Stents?

Author(s): 

Morton Kern, MD, Clinical Editor, Professor of Medicine, Associate Chief Cardiology, University of California Irvine, Orange, California
mortonkern005@hotmail.com

Note: This article contains corrected information (at the bottom asterisk).

I have had the good luck and opportunity to be able to discuss problems via an email
forum with a large number of prominent interventional colleagues to understand their opinions and obtain insights into some thorny or unusual cath lab conundrums. One recent issue was raised by Dr. Zoltan Turi, Director, Cooper Vascular Center, of Cooper University Hospital in Camden, New Jersey. He asked, “Have you dealt with nickel allergy and coronary stents? Not atrial septal defect (ASD) devices, but the usual coronary stents in the patient needing a drug-eluting stent (DES)? The literature is not clear on whether nickel allergy is associated with adverse outcomes. Of note, 15% of the population tests positive for nickel sensitivity.1 Most case reports are contaminated by other possible culprits. What’s your experience?”

I emailed my colleagues the following questions:

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?

Before I provide their answers, here’s what I learned about nickel allergy from the Mayo Clinic website. Nickel allergy is one of the most common causes of allergic contact dermatitis and is often associated with earrings and other jewelry for body piercings. It can affect people of all ages and usually develops after repeated or prolonged exposures. Once nickel allergy develops, one will always be sensitive to the metal and should avoid contact. Nickel-related contact dermatitis usually begins within 12 to 48 hours after exposure and can persist for two to four weeks with symptoms that also can include a skin rash, itching, redness, and dry skin patches resembling a burn, occasionally with blisters and draining fluid in severe cases.

Certain factors increase the risk of developing a nickel allergy, which include body piercings, working with metal, being female [probably because females tend to have more piercings (just a guess)], having a family history of nickel allergy, being allergic to other metals, and undergoing patch testing. Interestingly, during patch testing, very small quantities of potential allergens (including nickel) are applied to the skin to check for a reaction. Please note that because of the low concentrations of allergens used, patch tests are safe even for people with severe allergies.

Nickel allergy and headaches?

Dr. Tobis and colleagues from UCLA have written about ASD devices and nickel allergy.2 They reported such an association in 37 patients who had ASD or patent foramen ovale (PFO) closure with an Amplatzer (AGA Medical, Golden Valley, Minn.) device which is composed of nitinol, an alloy containing nickel and titanium in roughly equal atomic percentages.

The patients received nickel allergy patch testing with the TRUE skin test3 either before or after defect closure. Of the 150 patients who received either an ASD or PFO closure device, 62 (41%) had chest pain, palpitations, or increased migraine headaches (MHA). Nickel patch testing was available in 37 patients. There were seven patients (5%) who noted new-onset MHA or increased frequency and severity of MHA or aura post-procedure. Of 6 patients who were tested for nickel allergy, 4 had a positive nickel skin test. The most important observation of this study was that 67% of the patients who had new onset or increased frequency and severity of MHA tested positive for nickel hypersensitivity.

Nickel allergy in stented patients?

The incidence of nickel allergy to coronary stents is less clear. From the forum editor for Angioplasty.Org, October 17, 2010: “allergic reactions to small implanted devices such as coronary stents, where the actual amount of metal is quite small, have not been well-studied. Some cardiologists are fairly sure that some patients have hypersensitivity reactions to the plastic polymers used in first generation drug-eluting stents (Taxus, Cypher) but hypersensitivity reactions to the metal, especially nickel, are not well-documented, even though all of the FDA-required package inserts for coronary stents specifically state that their use is contra-indicated in patients who are allergic to any of the device’s components, and specifically to nickel or surgical stainless steel 316.”

Does nickel allergy cause in-stent restenosis?

Dr. Marc Feldman at the Health Science Center, University of Texas, San Antonio, is currently conducting a research study on allergic reactions to drug-eluting stents. When asked, he replied, “Nickel allergies are a different type of allergic reaction than what we are investigating. Patients with nickel allergies developed increased intimal hyperplasia and restenosis with bare metal stents, but there were no reports of eosinophilic reactions.” Dr. Feldman was referring to a German study4 from The Lancet in 2000 which examined 131 patients with 171 stents 6 months after stent implantation and underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and small 316L stainless-steel plates. In-stent restenosis occurred in 89 patients. All 10 patients with positive patch-test results had restenoses. Four male patients had positive reactions to molybdenum, and seven patients (four male, three female) had reactions to nickel. No patient with an allergic reaction to the standard test substances had a positive reaction to the stainless-steel plates. All patients with positive results had recurrent angina pectoris and needed target-vessel revascularization. They concluded that allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent restenosis.

However, Dr. Greg Stone from Columbia University, NYC, commented, “Most studies have not found a relationship between nickel allergy and restenosis.5,6 Really, there’s not much of quality written on this [subject].”

Should you test for nickel allergy?

A cardiologist from Emory University replied, “I polled some of my colleagues and they said that they were aware of some concerns, but had not seen definitive evidence. We do not test for Ni allergy.”

From Duke University: “I have never tested anybody for nickel allergy. I am not sure what I would do with it, if they would be positive.”

From Rush University: “Some years ago, I had a patient who had a skin allergy to nickel. Initially I did a balloon angioplasty only. It restenosed. Then I placed one of those gold stents. It restenosed. Then I did brachytherapy and cutting balloon. It still restenosed. Then I sent the patient for an IMA [internal mammary artery graft]. She has been fine for the past 10 years.”

From the Mayo Clinic: “We don't routinely test for nickel allergy. However, the stent package labeling clearly states that stents should not be used in patients with known hypersensitivity, and I don't know how you get around that label, even though I think there is little or weak data on this subject (i.e., The Lancet article). The amount of nickel varies, but even the cobalt-chromium stents have 11% nickel. Abbott Laboratories has a nickel testing package that they can send to you overnight if you want to test a patient.” Another cardiologist from the Mayo Clinic reported, “I have mainly disregarded this in the past. There was a Lancet article4 several years ago about skin testing which identified that in a small series of patients, those with a positive skin test had more restenosis.” A third cardiologist from the Mayo Clinic added, “I, too, have generally ignored this in the past. Since there is a relatively high rate of Ni allergy in community, I would assume any signal of problem in the 1.5 million patients who get stents in U.S. annually would have been seen by now.”

Dr. Tobis from UCLA commented, “Just before the DES stents came out, there was a report from Germany4 demonstrating a high incidence of nickel allergy in patients who develop restenosis with bare metal stents. This makes a lot of sense to me. We don’t see this as much with the DES, so, no, I do not test patients for nickel allergy who get stents. On the other hand, for ASD patients, I do test for nickel allergy, especially in women who give a history of inability to wear anything but pure silver or gold earrings. For PFO patients, we have successfully used the Helex device (Gore Medical, Flagstaff, Arizona) in patients who test positive for nickel allergy using the TRUE skin patch test.”

From St. Vincent Hospital in Worcester, Mass.: “I assume stent-related nickel allergy theoretically could be an issue. I’m not sure how I would identify people at risk. I certainly don’t know how I would test [for Ni allergy] since I don’t know if there is a reliable test that would correlate with intravascular responsiveness. Bottom line, I don’t test for nickel allergy, don’t treat for it, and don’t pick stents based on any concern about it.” A similar opinion was provided by cardiologists from the University of Illinois.

What about CABG in nickel allergic patients?

From Eureka, Ca.: “Since DES arrived, my concern about nickel allergy abated. I don't do skin testing for nickel before stenting, and it does not impact my choice of stent. Like UCLA, I test all PFO/ASD patients prior to implantation; and use the Helix device in nickel-allergic patients rather than Amplatzer. However, if a patient with known nickel allergy is referred for cardiac surgery, I ask the surgeon not to use traditional sternal wires. There is a very high nickel content in sternal wires, and this has been associated with Dressler’s syndrome in those with nickel allergy."7

From Lenox Hill, NYC: “When I saw the subject of the email was ‘Question regarding nickel for interventional procedures,’ I thought this was about another round of Medicare reimbursement reductions. Now that I know we’re talking about allergy, this has been a bigger concern for orthopedists who have worried that heightened inflammation around nickel-containing artificial joints might make them loose, but a recent analysis suggests it’s not a problem for hip joints.8

From Switzerland: “To my knowledge, the average European cardiologist, like me, is aware of the Lancet paper,4 but, like others, I have neglected the issue. To answer the questions: 1) no, to testing and 2) no, to a particular attitude in selecting stents, but the question remains open.”

From Ochsner Clinic: “We usually ignore nickel allergies in coronary stent patients. I have never seen a reaction that I attributed to a nickel allergy. I do ask the question in structural heart repair and it is a required question in the structural device trials in which we participate. I have sent one patient for surgical repair of an ASD due to a jewelry allergy since the mid 1990’s. I guess I did the right thing, but I’m not sure.” Another cardiologist at Ochsner added, “I came across this issue once while I was a cardiology fellow. We and the allergists took an old bare metal stent off the shelf and skin tested her with it. We literally strapped it to her thigh for 24 hours. She had no reaction. So we stented her. She did fine.”

Does one stent have more nickel than others?

From Quebec City: “I have learned from Dr. Adnan Kastrati some years ago that many German centers systematically evaluate skin reaction to nickel prior to procedure. We never changed our procedure, since we were told that skin reaction would not necessarily predict anything. When we asked the companies, it seemed that the bare metal stent from Medtronic contained less nickel than the Vision stent.* Maybe the new Boston Scientific platinum stent could be an option in such a case.”

The bottom line

The bottom line for me and most of the respondents to my 3 starting questions was a triple NO for coronary stents (not ASD/PFO). NO, I don’t test for nickel allergy. NO, I don’t treat patients for nickel allergy. And, finally, NO, I don’t pick stents based on fear of allergy. I thank those cardiologists brave enough to give us their honest opinion and I hope you learned as much as I did on nickel allergy and what to do when you think this is a problem.

References

1. Marks Jr. JG, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group patch-test results, 1998 to 2000. Am J Contact Dermatol 2003;14:59–62.

2. 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;47:1226–1227.

3. Zug KA, Warshaw EM, Fowler JF Jr, et al. Patch-test results of the North American Contact Dermatitis Group 2005-2006. Dermatitis 2009 May-Jun;20(3):149–160.

4. Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000;2;356(9245):1895–1897.

5. Tohoku J. Is there a link between nickel allergy and coronary stent restenosis? Exp Med 2005;206:243–246.

6. Nakazawa G, Tanabe K, Aoki J, et al. Sirolimus-eluting stents suppress neointimal formation irrespective of metallic allergy. Circ J 2008;72:893–896.

7. Fine PG, Karwande SV. Sternal wire-induced persistent chest pain: a possible hypersensitivity reaction. Ann Thorac Surg 1990;49(1):135–136.

8. Thyssen JP, Jakobsen SS, Engkilde K, et al. The association between metal allergy, total hip arthroplasty, and revision: A case-control study. Acta Orthop 2009 December 4;80(6):646–652.

*Update: The Medtronic website offers a downloadable PDF called “Advantages of Cobalt Alloy for Coronary Stents” (Available at http://wwwp.medtronic.com/newsroom/content/1110132739468.pdf) which states that the chemical composition for the alloy in the Driver stent (which is the same alloy used for Medtronic’s Integrity stent) has 35% nickel content. In comparison, the alloy used in the Vision stent has approximately 10% nickel content. For additional information on the metal composition of Abbott stents, visit the Abbott Vascular website: (http://www.abbottvascular.com/static/cms_workspace/pdf/coronary_interven...).

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