Nickel Allergy and the Amplatzer Septal Occluder

Transcatheter device closure of atrial septal defect (ASD) is an alternative to surgical closure. Currently, the Amplatzer Septal Occluder (ASO) (AGA Medical Corp, Golden Valley, Minnesota) is the only device approved for ASD closure in the United States. Several other closure devices are available in study protocols. Nitinol, an alloy composed of 55% nickel and 45% titanium1,2 is a component of many devices. The ASO contains the greatest amount of nickel. We report a case of nickel allergy that altered our choice of device for transcatheter ASD closure. Case Report. A 54-year-old woman was referred for transcatheter closure of a 16 mm ostium secundum ASD using the ASO. Although she previously denied medical allergies, on the morning of the procedure, she reported that her skin “reacted to certain jewelry.” Due to a potential nickel allergy, the procedure was cancelled and it was decided to test the patient for cutaneous reactivity to the ASO. A 20 mm ASO was attached to her left forearm under a tegaderm patch (3M, St. Paul, Minnesota). Another tegaderm patch was affixed to her right forearm as a control. After just 12 hours of contact, cutaneous erythema and swelling developed beneath the device (Figure 1). The device was removed and blistering of the skin was noted for the next 24 hours. Similar testing was performed using the CardioSEAL (Nitinol Medical Technologies, Boston, Massachusetts) and Cardia (Cardia, Burnsville, Minnesota) devices. After 72 hours, no cutaneous reaction occurred with either of these devices. The patient’s 17 mm stretched diameter ASD was successfully closed with a 33 mm CardioSEAL device. Discussion Approximately 8–10% of women and 1–2% of men are sensitized to nickel.³ Once sensitized, minor contact with metal containing nickel can cause a reaction.⁴ Repeated failure of nickel containing prosthetic heart valves,⁵ a higher incidence of coronary artery stent restenosis,⁶ and failure of nickel containing orthopedic and dental implants^7,8 have been reported in patients with nickel allergy. Patch testing is currently the gold standard for evaluating patients with allergic contact dermatitis.⁹ The classically positive patch test shows erythema, edema, and small, closely set vesicles that extend beyond the border of the patch.¹⁰ In this case, the patch test was interpreted as 2+/3+ based on erythema, edema, and vesicles at the site of testing. The MELISA Test, an optimized lymphocyte proliferative test, is also available for detecting metal sensitivity in patients with suspected allergy.¹¹ The relationship between cutaneous allergy and endocardial reaction is unknown. Nitinol, an alloy containing 55% nickel and 45% titanium, has the properties of thermal shape memory, superelasticity, corrosion resistance, and excellent biocompatibility making it ideal for use in implanted medical devices.^12,13 The ASO is made largely of nitinol. While the arms of the CardioSEAL contain MP35n (35% nickel)² and the arms of the Cardia device are made of nitinol, these devices contain less metal and therefore have less nickel than the ASO. Little is known about endocardial reactivity to nitinol in patients with nickel allergy. Ries et al. showed an increase in serum nickel levels after ASD device closure using the ASO in patients without nickel allergy; no adverse effects from increased nickel levels were found.¹ Vincent et al. reported possible nickel allergy four months after ASD closure using the HELEX septal occluder.¹⁴ The patient developed persistent itchiness of skin and soreness of feet and reacted positively to nickel skin patch testing. The consulting dermatologists thought the symptoms were consistent with an allergy to nickel. The device was subsequently explanted and the symptoms did not improve. Fukahara et al. reported a possible systemic allergic reaction to nickel two months after transcatheter closure of a patent foramen ovale (PFO) using a Cardia PFO-Star device.¹⁵ The patient reacted positively to nickel skin patch testing. Due to persistent high fever, edema, and elevated immunoglobulin E levels, the device was explanted 4 months after placement. Pathologic examination of the device showed nonspecific inflammatory changes with no eosinophilic infiltrate. After surgical closure of the PFO, the symptoms completely resolved. When questioned about allergies, patients frequently think of environmental or medical allergies. Potential metal allergies are often not reported. This case report describes a cutaneous allergic reaction to nickel contained in the ASO. The relationship between cutaneous allergy and endocardial reaction is currently unknown. We recommend that patients be questioned specifically about potential nickel allergy before transcatheter occlusion of ASD. Further study is needed to 1) determine endocardial reactivity to intracardiac devices in patients with nickel allergy, and 2) determine which patients with nickel allergy remain candidates for device closure of septal defects using nickel-containing devices.

1. Ries MW, Kampmann C, Rupprecht HJ, et al. Nickel release after implantation of the Amplatzer occluder. Am Heart J 2003;145:737–741. 2. Rahilly G, Price N. Nickel allergy and orthodontics. J Orthod 2003;30:171–174. 3. Sunderman F, Oskarson A. Nickel. In: Marian E. (ed). Metals and Their Compounds in the Environment: Occurrence, Analysis and Biologic Relevance. New York: VCH, 1991, pp.1101–1125. 4. ATSDR. Toxicology profile of Nickel. Agency for Toxic Substances and Disease Registry. Atlanta, Georgia, 1987. 5. Lyell A, Bain WH, Thomson RM. Repeated failure of nickel-containing prosthetic heart valves in a patient allergic to nickel. Lancet 1978;2: 657–659. 6. Koster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000;356:1895–1897. 7. Counts AL, Miller MA, Khakhria ML, et al. Nickel allergy associated with a transpalatal arch appliance. J Orofac Orthop 2002;63:509–515. 8. Gawkrodger DJ. Metal sensitivities and orthopedic implants revisited: The potential for metal allergy with the new metal-on-metal joint prostheses. Br J Dermatol 2003;148:1089–1093. 9. Belsito DV. Allergic Contact Dermatitis. In: Freedberg IM, Fitzpatrick TB, (eds.). Fitzpatrick’s Dermatology in General Medicine, 5th edition, Vol 1, 1999, pp.1447–1461. 10. Krafchik BR. 1995. Eczematous dermatitis. In: Schachner LA, Hansen RC, editors. Pediatric Dermatology 2nd edition, pp.685–721. 11. Valentine-Thon E, Schiwara HW. Validity of MELISA for metal sensitivity testing. Neuroendocrinol Lett 2003;24:57–64. 12. Barras CD, Myers KA. Nitinol — Its use in vascular surgery and other applications. Eur J Vasc Endovasc Surg 2000;19:564–569. 13. Gil FJ, Planell JA. Shape memory alloys for medical applications. Proc Inst Mech Eng 1998;212:473–488. 14. Vincent RN, Raviele AA, Diehl HJ. Single-center experience with the HELEX septal occluder for closure of atrial septal defects in children. J Intervent Cardiol 2003;16:79–82. 15. Fukahara K, Kazutomo M, Riess N, et al. Systemic allergic reaction to the percutaneous patent foramen ovale occluder. J Thorac Cardiovasc Surg 2003;125:213–214.