Coronary Restenosis and Contact Allergy to Stent Material

RE: Halwani DO, et al, In-vivo corrosion and local release of metallic ions from vascular stents into surrounding tissue. J Invasive Cardiol 2010;22:528–535.

Dear Editor,

In the article by Halwani et al, the interesting finding of transfer of heavy metal ions from stents into surrounding tissue is discussed due to the finding of the metal as such in vessels retrieved from patients with stents. In the article, the possible effect on inflammation and in-stent restenosis (ISR) is described. The already published finding that gold-coated stents have been associated with a considerable increase in the risk of ISR¹ and the putative effect of defects in the coating with the formation of galvanic elements and increased corrosion due to this are also discussed. In a large retrospective study in Sweden published in the British Journal of Dermatology in 2007² and in Contact Dermatitis in 2009,³ 484 patients stented with NIR stents (Boston Scientific Corp., Natick, Massachusetts) either without (NIR stents) or with gold coating (NIR Royal stents) were studied. The patients were asked to complete a questionnaire regarding their exposure to metals and their cardiac symptoms. Blood samples for analysis of gold were taken and the patients were then patch-tested to diagnose contact allergy. The patients had already been evaluated for restenosis by cardiologists (with no knowledge of the planned study). The two patient groups (stented with NIR stents and NIR Royal stents, respectively) were compared with each other and with a control group of sex- and aged-matched patients attending the department of dermatology for dermatitis. The aim was to confirm previous findings^4,5 that there was an increased risk of restenosis in gold stents and our previous findings⁶ of a high prevalence of contact allergy to gold in patients with gold stents. Another aim was to investigate a possible correlation between gold stents, contact allergy to gold and restenosis. The study did confirm that patients with gold stents run a higher risk of restenosis, and in the gold-stented patients a significantly higher frequency of contact allergy to gold compared to the control population (p 3 In patients stented with NIR Royal stents, we found a five-fold increased concentration of gold in blood compared to the patients stented with NIR stents,⁷ indicating a release of gold to the surrounding area from the stent. Regarding other stent materials (such as nickel, molybdenum, etc.), we found no significant correlation with contact allergy, although this has previously been reported in small materials.⁸ How then can there be a correlation between contact allergy to a metal and restenosis? Gold as a salt has been used to treat patients with rheumatoid arthritis, and it is well known that if the patient has a contact allergy to gold there may be systemic effects when exposed to gold in injections (fever and cytokine release).⁹ It is further known that gold as dental implants may give rise to local reactions known as lichenoid reactions around the material in the gingival.¹⁰ A metal can only give rise to a contact allergy in an ionized state, but we know that gold does corrode and form ions in contact with thiol groups, for instance.^11,12 These facts and our findings, we think, can explain that gold implants give rise to ions, possibly even more through the formation of galvanic elements due to mechanical damage to the surfaces in the stent in place. This increases the gold concentration locally as well as in blood, leading to a sensitization (if the patient has not been previously sensitized¹³ through dental material, for example) and further, through continuous release of ions, the elicitation of a contact allergic reaction in the shape of an “endothelitis” within the vessel where the stent is located.³ Contact allergy may thus, especially for metals known to have a large potential to form ions and induce contact allergy, be part of the explanation for restenosis in the stent area. As stent materials are constantly changing due to increasing needs for good biocompatibility and other desirable properties such as good visibility, it will be very difficult to perform a proper risk assessment in a prospective study with, for example, stainless steel stents to see if these also emit ions in amounts sufficient to induce contact allergy and possibly elicit a local reaction, an “endothelitis.” This ideal risk assessment seem difficult to perform, but perhaps the issue should be considered when choosing new stent materials so that care is taken to find materials where we do have some knowledge on how they perform as contact allergens. Cecilia Svedman, MD, PhD^*, Halvor Möller, MD, PhD^*, Carl Gunnar Gustavsson, MD, PhD^§, Magnus Bruze, MD, PhD^*

References

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2. Ekqvist S, Svedman C, Möller H, et al. High frequency of contact allergy to gold in patients with endovascular coronary stents. Br J Dermatol 2007;157:730–738.
3. Svedman C, Ekqvist S, Möller H, et al. A correlation found between contact allergy to stent material and restenosis of the coronary arteries. Contact Dermatitis 2009;60:158–164.
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8. Köster R; Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000;356:1895–1897.
9. Möller H. Clinical response to gold as a circulating contact allergen. Acta Derm Venereol 2000;80:111–113.
10. Ahlgren C, Bruze M, Möller H, et al. A case control study of contact allergy to gold in patients with oral lichen lesions. Submitted.
11. Flint GN. A metallurgical approach to metal contact dermatitis. Contact Dermatitis 1998;39:213–221.
12. Brown D, Smith W, Fox P, Sturrock R. The reactions of gold (0) with amino acids and the significance of these reactions in the biochemistry of gold. Inorg Chim Acta 1982;67:27–30.
13. Ahlgren C, Ahnlide I, Björkner B, et al. Contact allergy to gold is correlated to dental gold. Acta Derm Venereol 2002;82:41–44.

———————————————————— From the ^*Department of Occupational and Environmental Dermatology, SUS, Malmö, Lund University, Sweden and the ^§Department of Cardiology, SUS, Malmö, Lund University, Sweden The authors report no financial relationships or conflicts of interest regarding the content herein. Address for correspondence: Associate Professor Cecilia Svedman, Department of Occupational and Environmental Dermatology, Lund University, University Hospital SUS, 20502 Malmö, Sweden. Email: cecilia.svedman@skane.se