REVIEW ARTICLE
Nickel Hypersensitivity in Patients with Inferior Vena Cava Filters: Case Report and Literature and MAUDE Database Review Maud M. Morshedi, MD, PhD, and Thomas B. Kinney, MD, FSIR
ABSTRACT Placement of a prophylactic retrievable inferior vena cava (IVC) filter was requested in a 73-year-old woman with nickel hypersensitivity resulting in a clinical dilemma. Given that all retrievable filters contain nickel, the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database were reviewed; no documented case of IVC filter placement in a patient with nickel hypersensitivity or reported hypersensitivity reaction in a patient after IVC filter placement could be identified. This article presents the uneventful course of the case described and a review of the literature and recommendations on use of nickel-containing devices in patients with nickel hypersensitivity.
ABBREVIATIONS IVC = inferior vena cava, MAUDE = Manufacturer and User Facility Device Experience
CASE REPORT Clinical History Institutional review board approval was obtained for retrospective collection of depersonalized data from electronic medical records and picture archival computed systems. This study is compliant with the Health Insurance Portability and Accountability Act of 1996. A 73-year-old woman with mucinous adenocarcinoma of the appendix underwent cytoreduction surgery with heated intraperitoneal chemotherapy in 2008 and now presented with recurrence on surveillance imaging. The patient had been placed on lifelong prophylactic warfarin (Coumadin) therapy because of a pulmonary embolism after her surgery in 2008. In 2012, the Interventional Radiology service was consulted to place a prophylactic inferior vena cava (IVC) filter before repeat cytoreductive surgery with heated intraperitoneal chemotherapy. Her medical history was noncontributory
From the Department of Radiology, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8756. Received February 11, 2014; final revision received April 13, 2014; accepted April 21, 2014. Address correspondence to M.M.M.; E-mail: maud.morshedi@my. rfums.org M.M.M. is a paid consultant for Surefire Medical. T.B.K. is the chairman of DSMB for Crux Biomedical. & SIR, 2014. Published by Elsevier Inc. All rights reserved. J Vasc Interv Radiol 2014; 25:1187–1191 http://dx.doi.org/10.1016/j.jvir.2014.04.017
except for a history of asthma and multiple food and drug allergies, including a rash with penicillins, anaphylaxis to shellfish, and contact dermatitis with nickel products.
Clinical Course Because all currently available retrievable IVC filters contain nickel (Table), with most composed of nitinol (56% nickel), the patient and our team were concerned about a possible allergic reaction to the filter. A discussion was held whether to place a permanent 316L stainless steel Greenfield filter, although this was also noted to contain 10%–14% nickel, or a titanium alloy Greenfield filter (Boston Scientific Corporation, Natick, Massachusetts), but the primary team excluded its use preferring a retrievable option. A retrievable filter was preferred because it could potentially be removed in the event of an allergic reaction. A Conichrome (cobaltchromium-nickel-molybdenum-iron alloy containing 15.4% nickel; Fort Wayne Metals, Fort Wayne, Indiana) Gunther Tulip retrievable IVC filter (Cook, Inc, Bloomington, Indiana) was placed without complication in the infrarenal IVC before surgery. Given her history of anaphylaxis to an allergen, the patient was premedicated per Radiology Department policy with prednisone and diphenhydramine before the procedure for prophylaxis against possible allergic reaction to intravenous contrast medium. The patient was given no additional immunosuppressive or antiallergenic medications during the course of her care and experienced no adverse reactions to the IVC filter
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Table . Metal Composition and Nickel Content by Weight of Commonly Used U.S. Food and Drug Administration–Approved IVC Filters* Filter Material Trade Name (Metal
Approximate Nickel
Composition)
Composition (Weight %)
Filter Name (Manufacturer) Retrievable Filters ALN (ALN Implants Chirurgicaux)
316L stainless steel (iron-chromium-
Recovery/G2 (Bard Peripheral Vascular)
nickel-molybdenum) Nitinol (nickel-titanium)
10–14 56
G2X (Bard Peripheral Vascular)
Nitinol (nickel-titanium)
56
Denali (Bard Peripheral Vascular) Eclipse (Bard Peripheral Vascular)
Nitinol (nickel-titanium) Nitinol (nickel-titanium)
56 56
Meridian (Bard Peripheral Vascular)
Nitinol (nickel-titanium)
Gunther Tulip (Cook, Inc)
Conichrome (cobalt-chromium-nickelmolybdenum-iron)
15.4
Celect (Cook, Inc)
Conichrome (cobalt-chromium-nickel-
15.4
OPTEASE (Cordis Corporation)
molybdenum-iron) Nitinol (nickel-titanium)
56
Option (Rex Medical)
Nitinol (nickel-titanium)
56
SafeFlo (Rafael Medical Technologies) Crux (Volcano Corporation)
Nitinol (nickel-titanium) Nitinol (nickel-titanium)
56 56
56
Permanent Filters Vena Tech LGM (B. Braun Medical, Inc)
Phynox (cobalt-chromium-nickelmolybdenum-iron)
15–18
Vena Tech LP (B. Braun Medical, Inc)
Phynox (cobalt-chromium-nickel-
15–18
Simon Nitinol (Bard Peripheral Vascular)
molybdenum-iron) Nitinol (nickel-titanium)
Bird’s Nest (Cook, Inc)
304 stainless steel (iron-chromium-nickel-
TRAPEASE (Cordis Corporation)
molybdenum) Nitinol (nickel-titanium)
Greenfield (Boston Scientific Corporation)
316L stainless steel (iron-chromiumnickel-molybdenum) Beta III titanium alloy (titanium-
56 8–10.5 56 10–14 0
molybdenum-zirconium-tin) *ALN Implants Chirurgicaux (Bormes les Mimosas, France); Bard Peripheral Vascular (Tempe, Arizona); Cook, Inc (Bloomington, Indiana); Cordis Corporation (Hialeah, Florida); Rex Medical (Conshohocken, Pennsylvania); Rafael Medical Technologies (Dover, Delaware); Volcano Corporation (San Diego, California); B. Braun Medical, Inc (Bethlehem, Pennsylvania); Boston Scientific Corporation (Natick, Massachusetts).
immediately after placement or during the course of her hospital stay. She was followed for the next month, and no evidence of a usual or unusual hypersensitivity reaction was found. The filter was retrieved without difficulty 36 days after placement. No symptomatic thromboembolic events were documented.
DISCUSSION Per the manufacturer guidelines, a relative contraindication to placement of a nickel-containing IVC filter is hypersensitivity to nickel, and manufacturers warn that a patient may experience an allergic response. Nickel is the most common occupational and public contact allergen affecting approximately 8.6% of the population, disproportionately so in women (1,2). According to the National Hospital Discharge Survey, from 2006–2010,
approximately 536,000 IVC filters were placed at about 239 hospitals throughout the United States, 265,000 in men and 271,000 in women (3). Based on this reported prevalence, approximately 50,000 of these patients would be expected to have nickel hypersensitivity. However, a review of the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration provides neither a documented case of IVC filter placement in a patient with nickel hypersensitivity nor a reported hypersensitivity reaction in a patient after placement of an IVC filter. The published literature was reviewed by performing a keyword search in PubMed for terms describing allergy/hypersensitivity reactions to IVC filters (keywords “IVC,” “venous,” “vena cava,” “filter,” “nickel,” “metal,” “hypersensitivity,” “allergy,” “allergies,” “allergic”). Potentially relevant articles were retrieved and reviewed along with
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their reference lists to find studies that the search strategy may have missed. The MAUDE database simple query was also searched during all available years in the database (1992–2013) using the above-listed keywords for possible hypersensitivity reactions associated with the use of currently approved IVC filters. Because of this high population prevalence of nickel hypersensitivity and the increasing use of nickelcontaining IVC filters and other endovascular devices, we review the published literature on the use of implantable nickel-containing devices in patients with nickel hypersensitivity and discuss how these finding may translate to the placement of IVC filters. No published literature specifically discusses IVC filters in patients with nickel hypersensitivity; however, correlate studies and case reports with other nickel-containing devices such as the Essure sterilization device (Bayer AG, Leverkusen, Germany), AMPLATZER Occluder (St. Jude Medical, Inc, St. Paul, Minnesota), vascular and nonvascular stents, and other endovascular and implantable devices are available (1,4–19). Nickel allergy is a type IV (delayed type) hypersensitivity reaction, which, in contrast to the other hypersensitivity types, is not an antibody-mediated reaction but rather a cell-mediated response using CD4þ and CD8þ T cells (1,20). The primary manifestation of nickel hypersensitivity is contact dermatitis characterized by inflamed, pruritic, and erythematous skin most commonly found at the site of contact, but it can also manifest at distant sites. Nickel hypersensitivity can also manifest as eczema, urticaria, vasculitis, chronic inflammation, fever, pain, edema, cardiac arrhythmia, pericardial effusion, respiratory issues, poor wound healing, and device failure, which has most commonly been defined as device loosening for joint prostheses, instent stenosis or restenosis for endovascular or biliary stents, or any of the listed reactions severe enough to warrant device removal (1,6,9,17). Metal ions are too small to act directly as allergens. Nickel ions act as haptens, altering tissue proteins to become allergenic. Nickel hypersensitivity is not triggered by dietary intake but rather skin exposure to metal, which sensitizes the patient to future exposure (1,19). The increasing incidence of nickel allergies is thought to be directly related to the increasing number of ear piercings, which is also why it is thought to be more common in women than men (1). The most comprehensive review to date on hypersensitivity induced by a nickel-containing device concerned the nitinol Essure contraceptive device in women (19). The reported incidence of suspected nickel hypersensitivity–related adverse events was 0.01% of the 4 400,000 devices sold in the United States during the 9-year study period. The incidence of confirmed nickel reactions was even smaller. An additional European study reported a 0.05% incidence of confirmed nickel reactions after 4,242 placements of the Essure
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device (12). This study included 25 women with known nickel allergy, none of whom developed a proven hypersensitivity reaction (5). The extremely low incidence of device-related hypersensitivity reactions despite the high incidence of nickel allergy is speculated to be due partly to the very low levels of nickel ion released into blood by nitinol (19). In vitro studies have shown that nitinol devices release significantly less nickel into the surrounding medium than cobalt-chromium or stainless steel despite the greater proportion of nickel in the composition of nitinol devices (21). The average amount of natural nickel ingested daily from food and water is 300 μg/d; the highest measured rate of serum nickel from an Essure microinsert was found to be 0.14 μg/d, a quantity almost 2,000-fold less than dietary intake. The Essure data demonstrate an almost negligible occurrence of proven nickel-related reactions. This paucity of nickel-related reactions has also proven true for endovascular devices, where direct exposure to the bloodstream is most likely to result in nickel ion release and subsequent allergic reaction. A review by Honari et al (9) found that nickel hypersensitivity reactions are uncommon with endovascular devices, which was supported by a review by Schram et al (1) suggesting a risk factor for nitinol-related nickel allergy of 1 in 17,000. Ekqvist et al (7), studying 460 patients with coronary artery stents, found that there was no correlation between serum nickel concentration and nickel patch test reaction. Additionally, median serum nickel concentration in their study was 0.669 ng/ mL, which is minimally elevated from normal serum nickel concentration (0.14–0.65 ng/mL) (22) with reference values of o 2 ng/mL considered normal and values 4 10 ng/mL considered toxic (23,24), again suggesting that very low levels of nickel are released from these devices. A study of 67 patients with no history of nickel allergy by Ries et al (16) found mean serum nickel concentration increased from 0.47 ng/mL before implantation to 1.27 ng/mL within 24 hours after transcatheter closure of atrial septal defects with the AMPLATZER Occluder device with a maximum mean serum concentration of 1.5 ng/mL seen 1 month after implantation. However, no hypersensitivity reactions or device failure was observed. The mean serum nickel concentration decreased at 3 months and 1 year after implantation to a low of 0.25 ng/mL, which was hypothesized to be due to a protective titanium oxide and calcium phosphate coat insulating the implant and limiting nickel release as previously shown in in vitro studies (25). Reddy et al (14) evaluated 95 patients after transcatheter atrial septal closure with the GORE HELEX device (W.L. Gore and Associates, Inc, Newark, Delaware), including 89 patients with no known history of nickel allergy and 6 patients with positive skin testing. None of the patients with positive skin testing showed allergic reactions after implantation, and only 1 of the 89 patients (1%) with no known history
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of nickel allergy showed an allergic reaction after implantation. In contrast, a study by Rigatelli et al (17) found that eight of nine patients with positive skin patch testing for nickel allergy developed allergic symptoms 1–2 days after implantation with either an AMPLATZER Occluder device or Premere Closure System (St. Jude Medical, Inc). These allergic reactions lasted up to 5 weeks after implantation, although nearly all resolved within 2 weeks after 7 days of empiric treatment with prednisone and clopidogrel. The remaining 37 patients with negative skin patch testing for nickel allergy showed no evidence of nickel allergy after device implantation. It has been suggested that the incidence of nickel allergy to implantable cardiac devices is negligible despite the high prevalence of nickel allergy in the general population, given that 4 55,000 cardiac defect closure devices have been implanted worldwide, and proven cases of implantation-related nickel allergy remain extremely rare (4,10). Of particular note for interventional radiologists, there has been only one reported case in the literature to date of an allergic reaction following the placement of a superficial femoral artery nitinol stent in a patient with known nickel allergy (26). Although the patient’s symptoms were refractory to medical therapy, the symptoms resolved after stent explantation. According to the National Hospital Discharge Survey, from 2006–2010, approximately 306,000 non–drug-eluting peripheral stent insertion procedures were performed at about 239 hospitals throughout the United States (3), leading one to expect a much larger prevalence of hypersensitivity reactions after stent placement. The paucity of reported clinical manifestations of nickel allergy after peripheral arterial stent placement suggests that although reactions may be severe, the frequency of clinically relevant reactions remains extremely low. In addition, reports available to date show metal-induced hypersensitivity reactions to coronary stents are also extremely rare with the major but debated concern being in-stent restenosis (9), a reaction that needs further evaluation for peripheral arterial stents but is of less concern with intravenous devices such as IVC filters. Other intravascular devices, such as implantable pacemakers and cardioverterdefibrillators, valvular devices, and aortic endografts, have also been associated with allergic reactions, but most reports are rare or anecdotal (9).
Screening for Metal Allergy The mechanism of hypersensitivity reaction to implanted metallic devices has yet to be fully elucidated because insufficient evidence exists to confirm that a type IV hypersensitivity reaction is involved, although that is the assumed mechanism. Despite the paucity of data and the lack of a reliable test to predict implantable device-related nickel hypersensitivity, some authors still suggest baseline screening for all patients (9,15).
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Patch testing is the gold standard for the evaluation of type IV hypersensitivity reactions; however, not all patients with a positive patch test are clinically symptomatic, and many who report nickel hypersensitivity fail the patch test (18). An abbreviated series can be used in patients without a history of contact dermatitis, but full allergen evaluation is recommended for patients with reported dermatitis. Comprehensive allergen testing is needed, not testing against only a single allergen, because multiple sources of dermatitis can exist from the various device components. An extended series of patch testing has been recommended to include metals commonly present in endovascular devices in patients with suspected metal allergy. Additionally, the test should be performed using adequate amounts of allergen and not just lowest concentration. The device material also may be tested directly on the patient’s skin to evaluate for hypersensitivity reactions. A test kit is sometimes available from the device manufacturer for this purpose; however, the provided test disks are not always adequate to prove a reaction. False-positive pressure effects and false-negative reactions may occur alongside irritant or other questionable reactions from the material (15,18,27).
Recommended Management for Device Placement in Patients with Nickel Allergy No evidence-based management recommendations exist; however, management routines have been proposed by various authors. Meier (11) suggested that nothing needs to be done before device implantation. In contrast, Thomas et al (28) described a German consensus to use titanium implants for all patients with metal allergy, and Lai et al (10) suggested a tapered oral dose of prednisone over 21 days for all patients with suspected metal allergy. In reviewing the previously proposed management regimens, Schalock et al (18) recommended a management algorithm. They proposed that no action is required if a patient with a positive patch test has no allergic symptoms after implant placement. If the patch test is positive and the patient is symptomatic after implant placement, the implant should be removed, as long as it is safe and feasible, and replaced with a nonallergenic alloy. However, if the implant cannot be removed, a 21-day tapered course of oral prednisone should be considered. Despite the varying opinions on management, most authors agree that a positive patch test and a positive history of nickel allergy should not automatically preclude a patient from receiving a medically needed metal device.
CONCLUSIONS The patient described in the present article had no adverse reaction to the nickel-containing IVC filter after placement for 36 days despite reported nickel contact
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dermatitis. No formal skin patch testing was performed to confirm her allergy. Nevertheless, despite the controversy in the literature regarding the relationship of nickel contact dermatitis and systemic response to nickel, most authors agree that nickel allergy is unlikely to be a true contraindication to placement of a nickelcontaining device. Lending support to this hypothesis is the finding that there are no reported incidents of nickel allergy to IVC filter placement to date despite the high prevalence of nickel allergy in the general population and large numbers of filters placed. Having reviewed the literature and given the rarity of reactions to endovascular devices, placing nickel-containing IVC filters as medically indicated in patients regardless of nickel allergy history does not appear to be contraindicated. Use of retrievable IVC filters in these patients is recommended because such filters potentially can be removed in the event of an allergic reaction, which appears to resolve symptoms in nearly all reported cases of allergic reaction to implantable metallic devices. Treating physicians may follow the recommended screening and treatment guidelines suggested by Schalock et al (18) before placement, but no scientific data support this screening, which is based on anecdotal recommendations. Evaluation of the incidence of nickel allergy with IVC filters and a more rigorous evaluation of the screening tools and their role in predicting allergic response to nickel-containing devices need to be performed. Creation of a prospective database for reporting allergic reactions and subsequent clinical course in patients with nickel allergy after IVC filter placement may be a first step toward elucidating the true effect of this phenomenon. In the present case, the patient was also driving the concern about her nickel allergies and whether the nickel-containing IVC filter would cause her problems. It is conceivable that other physicians may be aware of a nickel allergy in a patient needing an IVC filter who may be concerned about whether this is an issue with the current generation of devices. As physicians implanting such devices, the message to convey to patients is the relatively safe profile of inserting such devices as evidenced by the absence of documented problems despite so many insertions as well as the availability of retrievable options in the rare case of an allergic reaction.
REFERENCES 1. Schram SE, Warshaw EM, Laumann A. Nickel hypersensitivity: a clinical review and call to action. Int J Dermatol 2010; 49:115–125. 2. Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population—prevalence and main findings. Contact Dermatitis 2007; 57:287–299. 3. National Hospital Discharge Survey 1965-2010. Atlanta: Centers for Disease Control and Prevention; 2012. 4. Anselmino M, Ribezzo M, Orzan F. Nickel allergy, how deep? Acta Cardiol 2009; 64:104–106
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5. Arjona JE, Velasco E, Povedano B, Castillo R, Davalos S. Complications associated with the Essure device: analysis after 4000 procedures. Gynecol Surg 2010; 7:S89. 6. Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis 2011; 22:65–79. 7. Ekqvist S, Svedman C, Lundh T, Moller H, Bjork J, Bruze M. A correlation found between gold concentration in blood and patch test reactions in patients with coronary stents. Contact Dermatitis 2008; 59: 137–142. 8. Gimenez-Arnau A, Riambau V, Serra-Baldrich E, Camarasa JG. Metalinduced generalized pruriginous dermatitis and endovascular surgery. Contact Dermatitis 2000; 43:35–40. 9. Honari G, Ellis SG, Wilkoff BL, Aronica MA, Svensson LG, Taylor JS. Hypersensitivity reactions associated with endovascular devices. Contact Dermatitis 2008; 59:7–22. 10. Lai DW, Saver JL, Araujo JA, Reidl M, Tobis J. Pericarditis associated with nickel hypersensitivity to the Amplatzer occluder device: a case report. Catheter Cardiovasc Interv 2005; 66:424–426. 11. Meier B. Nickel allergy and device closure of the patent foramen ovale, now that we were told should we care? Catheter Cardiovasc Interv 2009; 74:652. 12. Povedano B, Arjona JE, Velasco E, Monserrat JA, Lorente J, CasteloBranco C. Complications of hysteroscopic Essure((R)) sterilisation: report on 4306 procedures performed in a single centre. BJOG 2012; 119:795–799. 13. Rabkin DG, Whitehead KJ, Michaels AD, Powell DL, Karwande SV. Unusual presentation of nickel allergy requiring explantation of an Amplatzer atrial septal occluder device. Clin Cardiol 2009; 32:E55–E57. 14. Reddy BT, Patel JB, Powell DL, Michaels AD. Interatrial shunt closure devices in patients with nickel allergy. Catheter Cardiovasc Interv 2009; 74:647–651. 15. Reed KB, Davis MD, Nakamura K, Hanson L, Richardson DM. Retrospective evaluation of patch testing before or after metal device implantation. Arch Dermatol 2008; 144:999–1007. 16. Ries MW, Kampmann C, Rupprecht HJ, Hintereder G, Hafner G, Meyer J. Nickel release after implantation of the Amplatzer occluder. Am Heart J 2003; 145:737–741. 17. Rigatelli G, Cardaioli P, Giordan M, et al. Nickel allergy in interatrial shunt device-based closure patients. Congenit Heart Dis 2007; 2: 416–420. 18. Schalock PC, Menne T, Johansen JD, et al. Hypersensitivity reactions to metallic implants—diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis 2012; 66:4–19. 19. Zurawin RK, Zurawin JL. Adverse events due to suspected nickel hypersensitivity in patients with essure micro-inserts. J Minim Invasive Gynecol 2011; 18:475–482. 20. Wang Y, Dai S. Structural basis of metal hypersensitivity. Immunol Res 2013; 55:83–90. 21. Messer RL, Wataha JC, Lewis JB, Lockwood PE, Caughman GB, Tseng WY. Effect of vascular stent alloys on expression of cellular adhesion molecules by endothelial cells. J Long Term Eff Med Implants 2005; 15: 39–47. 22. Templeton DM, Sunderman FW Jr, Herber RF. Tentative reference values for nickel concentrations in human serum, plasma, blood, and urine: evaluation according to the TRACY protocol. Sci Total Environ 1994; 148:243–251. 23. Nixon DE, Moyer TP, Squillace DP, McCarthy JT. Determination of serum nickel by graphite furnace atomic absorption spectrometry with Zeeman-effect background correction: values in a normal population and a population undergoing dialysis. Analyst 1989; 114:1671–1674. 24. Novelli EL, Rodrigues NL, Ribas BO. Superoxide radical and toxicity of environmental nickel exposure. Hum Exp Toxicol 1995; 14:248–251. 25. Wever DJ, Veldhuizen AG, de Vries J, Busscher HJ, Uges DR, van Horn JR. Electrochemical and surface characterization of a nickel-titanium alloy. Biomaterials 1998; 19:761–769. 26. Jetty P, Jayaram S, Veinot J, Pratt M. Superficial femoral artery nitinol stent in a patient with nickel allergy. J Vasc Surg 2013; 58:1388–1390. 27. de Fine Olivarius F, Menne T. Skin reactivity to metallic cobalt in patients with a positive patch test to cobalt chloride. Contact Dermatitis 1992; 27:241–243. 28. Thomas P, Schuh A, Ring J, Thomsen M. [Orthopedic surgical implants and allergies. Joint statement by the Implant Allergy Working Group (AK 20) of the DGOOC (German Association of Orthopedics and Orthopedic Surgery), DKG (German Contact Dermatitis Research Group) and DGAKI (German Society for Allergology and Clinical Immunology)]. Hautarzt 2008; 59:220–229.
Nickel Hypersensitivity in Patients with Inferior Vena Cava Filters: Case Report and Literature and MAUDE Database Review Maud M. Morshedi, MD, PhD, and Thomas B. Kinney, MD, FSIR
ABSTRACT Placement of a prophylactic retrievable inferior vena cava (IVC) filter was requested in a 73-year-old woman with nickel hypersensitivity resulting in a clinical dilemma. Given that all retrievable filters contain nickel, the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database were reviewed; no documented case of IVC filter placement in a patient with nickel hypersensitivity or reported hypersensitivity reaction in a patient after IVC filter placement could be identified. This article presents the uneventful course of the case described and a review of the literature and recommendations on use of nickel-containing devices in patients with nickel hypersensitivity.
ABBREVIATIONS IVC = inferior vena cava, MAUDE = Manufacturer and User Facility Device Experience
CASE REPORT Clinical History Institutional review board approval was obtained for retrospective collection of depersonalized data from electronic medical records and picture archival computed systems. This study is compliant with the Health Insurance Portability and Accountability Act of 1996. A 73-year-old woman with mucinous adenocarcinoma of the appendix underwent cytoreduction surgery with heated intraperitoneal chemotherapy in 2008 and now presented with recurrence on surveillance imaging. The patient had been placed on lifelong prophylactic warfarin (Coumadin) therapy because of a pulmonary embolism after her surgery in 2008. In 2012, the Interventional Radiology service was consulted to place a prophylactic inferior vena cava (IVC) filter before repeat cytoreductive surgery with heated intraperitoneal chemotherapy. Her medical history was noncontributory
From the Department of Radiology, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8756. Received February 11, 2014; final revision received April 13, 2014; accepted April 21, 2014. Address correspondence to M.M.M.; E-mail: maud.morshedi@my. rfums.org M.M.M. is a paid consultant for Surefire Medical. T.B.K. is the chairman of DSMB for Crux Biomedical. & SIR, 2014. Published by Elsevier Inc. All rights reserved. J Vasc Interv Radiol 2014; 25:1187–1191 http://dx.doi.org/10.1016/j.jvir.2014.04.017
except for a history of asthma and multiple food and drug allergies, including a rash with penicillins, anaphylaxis to shellfish, and contact dermatitis with nickel products.
Clinical Course Because all currently available retrievable IVC filters contain nickel (Table), with most composed of nitinol (56% nickel), the patient and our team were concerned about a possible allergic reaction to the filter. A discussion was held whether to place a permanent 316L stainless steel Greenfield filter, although this was also noted to contain 10%–14% nickel, or a titanium alloy Greenfield filter (Boston Scientific Corporation, Natick, Massachusetts), but the primary team excluded its use preferring a retrievable option. A retrievable filter was preferred because it could potentially be removed in the event of an allergic reaction. A Conichrome (cobaltchromium-nickel-molybdenum-iron alloy containing 15.4% nickel; Fort Wayne Metals, Fort Wayne, Indiana) Gunther Tulip retrievable IVC filter (Cook, Inc, Bloomington, Indiana) was placed without complication in the infrarenal IVC before surgery. Given her history of anaphylaxis to an allergen, the patient was premedicated per Radiology Department policy with prednisone and diphenhydramine before the procedure for prophylaxis against possible allergic reaction to intravenous contrast medium. The patient was given no additional immunosuppressive or antiallergenic medications during the course of her care and experienced no adverse reactions to the IVC filter
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Table . Metal Composition and Nickel Content by Weight of Commonly Used U.S. Food and Drug Administration–Approved IVC Filters* Filter Material Trade Name (Metal
Approximate Nickel
Composition)
Composition (Weight %)
Filter Name (Manufacturer) Retrievable Filters ALN (ALN Implants Chirurgicaux)
316L stainless steel (iron-chromium-
Recovery/G2 (Bard Peripheral Vascular)
nickel-molybdenum) Nitinol (nickel-titanium)
10–14 56
G2X (Bard Peripheral Vascular)
Nitinol (nickel-titanium)
56
Denali (Bard Peripheral Vascular) Eclipse (Bard Peripheral Vascular)
Nitinol (nickel-titanium) Nitinol (nickel-titanium)
56 56
Meridian (Bard Peripheral Vascular)
Nitinol (nickel-titanium)
Gunther Tulip (Cook, Inc)
Conichrome (cobalt-chromium-nickelmolybdenum-iron)
15.4
Celect (Cook, Inc)
Conichrome (cobalt-chromium-nickel-
15.4
OPTEASE (Cordis Corporation)
molybdenum-iron) Nitinol (nickel-titanium)
56
Option (Rex Medical)
Nitinol (nickel-titanium)
56
SafeFlo (Rafael Medical Technologies) Crux (Volcano Corporation)
Nitinol (nickel-titanium) Nitinol (nickel-titanium)
56 56
56
Permanent Filters Vena Tech LGM (B. Braun Medical, Inc)
Phynox (cobalt-chromium-nickelmolybdenum-iron)
15–18
Vena Tech LP (B. Braun Medical, Inc)
Phynox (cobalt-chromium-nickel-
15–18
Simon Nitinol (Bard Peripheral Vascular)
molybdenum-iron) Nitinol (nickel-titanium)
Bird’s Nest (Cook, Inc)
304 stainless steel (iron-chromium-nickel-
TRAPEASE (Cordis Corporation)
molybdenum) Nitinol (nickel-titanium)
Greenfield (Boston Scientific Corporation)
316L stainless steel (iron-chromiumnickel-molybdenum) Beta III titanium alloy (titanium-
56 8–10.5 56 10–14 0
molybdenum-zirconium-tin) *ALN Implants Chirurgicaux (Bormes les Mimosas, France); Bard Peripheral Vascular (Tempe, Arizona); Cook, Inc (Bloomington, Indiana); Cordis Corporation (Hialeah, Florida); Rex Medical (Conshohocken, Pennsylvania); Rafael Medical Technologies (Dover, Delaware); Volcano Corporation (San Diego, California); B. Braun Medical, Inc (Bethlehem, Pennsylvania); Boston Scientific Corporation (Natick, Massachusetts).
immediately after placement or during the course of her hospital stay. She was followed for the next month, and no evidence of a usual or unusual hypersensitivity reaction was found. The filter was retrieved without difficulty 36 days after placement. No symptomatic thromboembolic events were documented.
DISCUSSION Per the manufacturer guidelines, a relative contraindication to placement of a nickel-containing IVC filter is hypersensitivity to nickel, and manufacturers warn that a patient may experience an allergic response. Nickel is the most common occupational and public contact allergen affecting approximately 8.6% of the population, disproportionately so in women (1,2). According to the National Hospital Discharge Survey, from 2006–2010,
approximately 536,000 IVC filters were placed at about 239 hospitals throughout the United States, 265,000 in men and 271,000 in women (3). Based on this reported prevalence, approximately 50,000 of these patients would be expected to have nickel hypersensitivity. However, a review of the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration provides neither a documented case of IVC filter placement in a patient with nickel hypersensitivity nor a reported hypersensitivity reaction in a patient after placement of an IVC filter. The published literature was reviewed by performing a keyword search in PubMed for terms describing allergy/hypersensitivity reactions to IVC filters (keywords “IVC,” “venous,” “vena cava,” “filter,” “nickel,” “metal,” “hypersensitivity,” “allergy,” “allergies,” “allergic”). Potentially relevant articles were retrieved and reviewed along with
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their reference lists to find studies that the search strategy may have missed. The MAUDE database simple query was also searched during all available years in the database (1992–2013) using the above-listed keywords for possible hypersensitivity reactions associated with the use of currently approved IVC filters. Because of this high population prevalence of nickel hypersensitivity and the increasing use of nickelcontaining IVC filters and other endovascular devices, we review the published literature on the use of implantable nickel-containing devices in patients with nickel hypersensitivity and discuss how these finding may translate to the placement of IVC filters. No published literature specifically discusses IVC filters in patients with nickel hypersensitivity; however, correlate studies and case reports with other nickel-containing devices such as the Essure sterilization device (Bayer AG, Leverkusen, Germany), AMPLATZER Occluder (St. Jude Medical, Inc, St. Paul, Minnesota), vascular and nonvascular stents, and other endovascular and implantable devices are available (1,4–19). Nickel allergy is a type IV (delayed type) hypersensitivity reaction, which, in contrast to the other hypersensitivity types, is not an antibody-mediated reaction but rather a cell-mediated response using CD4þ and CD8þ T cells (1,20). The primary manifestation of nickel hypersensitivity is contact dermatitis characterized by inflamed, pruritic, and erythematous skin most commonly found at the site of contact, but it can also manifest at distant sites. Nickel hypersensitivity can also manifest as eczema, urticaria, vasculitis, chronic inflammation, fever, pain, edema, cardiac arrhythmia, pericardial effusion, respiratory issues, poor wound healing, and device failure, which has most commonly been defined as device loosening for joint prostheses, instent stenosis or restenosis for endovascular or biliary stents, or any of the listed reactions severe enough to warrant device removal (1,6,9,17). Metal ions are too small to act directly as allergens. Nickel ions act as haptens, altering tissue proteins to become allergenic. Nickel hypersensitivity is not triggered by dietary intake but rather skin exposure to metal, which sensitizes the patient to future exposure (1,19). The increasing incidence of nickel allergies is thought to be directly related to the increasing number of ear piercings, which is also why it is thought to be more common in women than men (1). The most comprehensive review to date on hypersensitivity induced by a nickel-containing device concerned the nitinol Essure contraceptive device in women (19). The reported incidence of suspected nickel hypersensitivity–related adverse events was 0.01% of the 4 400,000 devices sold in the United States during the 9-year study period. The incidence of confirmed nickel reactions was even smaller. An additional European study reported a 0.05% incidence of confirmed nickel reactions after 4,242 placements of the Essure
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device (12). This study included 25 women with known nickel allergy, none of whom developed a proven hypersensitivity reaction (5). The extremely low incidence of device-related hypersensitivity reactions despite the high incidence of nickel allergy is speculated to be due partly to the very low levels of nickel ion released into blood by nitinol (19). In vitro studies have shown that nitinol devices release significantly less nickel into the surrounding medium than cobalt-chromium or stainless steel despite the greater proportion of nickel in the composition of nitinol devices (21). The average amount of natural nickel ingested daily from food and water is 300 μg/d; the highest measured rate of serum nickel from an Essure microinsert was found to be 0.14 μg/d, a quantity almost 2,000-fold less than dietary intake. The Essure data demonstrate an almost negligible occurrence of proven nickel-related reactions. This paucity of nickel-related reactions has also proven true for endovascular devices, where direct exposure to the bloodstream is most likely to result in nickel ion release and subsequent allergic reaction. A review by Honari et al (9) found that nickel hypersensitivity reactions are uncommon with endovascular devices, which was supported by a review by Schram et al (1) suggesting a risk factor for nitinol-related nickel allergy of 1 in 17,000. Ekqvist et al (7), studying 460 patients with coronary artery stents, found that there was no correlation between serum nickel concentration and nickel patch test reaction. Additionally, median serum nickel concentration in their study was 0.669 ng/ mL, which is minimally elevated from normal serum nickel concentration (0.14–0.65 ng/mL) (22) with reference values of o 2 ng/mL considered normal and values 4 10 ng/mL considered toxic (23,24), again suggesting that very low levels of nickel are released from these devices. A study of 67 patients with no history of nickel allergy by Ries et al (16) found mean serum nickel concentration increased from 0.47 ng/mL before implantation to 1.27 ng/mL within 24 hours after transcatheter closure of atrial septal defects with the AMPLATZER Occluder device with a maximum mean serum concentration of 1.5 ng/mL seen 1 month after implantation. However, no hypersensitivity reactions or device failure was observed. The mean serum nickel concentration decreased at 3 months and 1 year after implantation to a low of 0.25 ng/mL, which was hypothesized to be due to a protective titanium oxide and calcium phosphate coat insulating the implant and limiting nickel release as previously shown in in vitro studies (25). Reddy et al (14) evaluated 95 patients after transcatheter atrial septal closure with the GORE HELEX device (W.L. Gore and Associates, Inc, Newark, Delaware), including 89 patients with no known history of nickel allergy and 6 patients with positive skin testing. None of the patients with positive skin testing showed allergic reactions after implantation, and only 1 of the 89 patients (1%) with no known history
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of nickel allergy showed an allergic reaction after implantation. In contrast, a study by Rigatelli et al (17) found that eight of nine patients with positive skin patch testing for nickel allergy developed allergic symptoms 1–2 days after implantation with either an AMPLATZER Occluder device or Premere Closure System (St. Jude Medical, Inc). These allergic reactions lasted up to 5 weeks after implantation, although nearly all resolved within 2 weeks after 7 days of empiric treatment with prednisone and clopidogrel. The remaining 37 patients with negative skin patch testing for nickel allergy showed no evidence of nickel allergy after device implantation. It has been suggested that the incidence of nickel allergy to implantable cardiac devices is negligible despite the high prevalence of nickel allergy in the general population, given that 4 55,000 cardiac defect closure devices have been implanted worldwide, and proven cases of implantation-related nickel allergy remain extremely rare (4,10). Of particular note for interventional radiologists, there has been only one reported case in the literature to date of an allergic reaction following the placement of a superficial femoral artery nitinol stent in a patient with known nickel allergy (26). Although the patient’s symptoms were refractory to medical therapy, the symptoms resolved after stent explantation. According to the National Hospital Discharge Survey, from 2006–2010, approximately 306,000 non–drug-eluting peripheral stent insertion procedures were performed at about 239 hospitals throughout the United States (3), leading one to expect a much larger prevalence of hypersensitivity reactions after stent placement. The paucity of reported clinical manifestations of nickel allergy after peripheral arterial stent placement suggests that although reactions may be severe, the frequency of clinically relevant reactions remains extremely low. In addition, reports available to date show metal-induced hypersensitivity reactions to coronary stents are also extremely rare with the major but debated concern being in-stent restenosis (9), a reaction that needs further evaluation for peripheral arterial stents but is of less concern with intravenous devices such as IVC filters. Other intravascular devices, such as implantable pacemakers and cardioverterdefibrillators, valvular devices, and aortic endografts, have also been associated with allergic reactions, but most reports are rare or anecdotal (9).
Screening for Metal Allergy The mechanism of hypersensitivity reaction to implanted metallic devices has yet to be fully elucidated because insufficient evidence exists to confirm that a type IV hypersensitivity reaction is involved, although that is the assumed mechanism. Despite the paucity of data and the lack of a reliable test to predict implantable device-related nickel hypersensitivity, some authors still suggest baseline screening for all patients (9,15).
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Patch testing is the gold standard for the evaluation of type IV hypersensitivity reactions; however, not all patients with a positive patch test are clinically symptomatic, and many who report nickel hypersensitivity fail the patch test (18). An abbreviated series can be used in patients without a history of contact dermatitis, but full allergen evaluation is recommended for patients with reported dermatitis. Comprehensive allergen testing is needed, not testing against only a single allergen, because multiple sources of dermatitis can exist from the various device components. An extended series of patch testing has been recommended to include metals commonly present in endovascular devices in patients with suspected metal allergy. Additionally, the test should be performed using adequate amounts of allergen and not just lowest concentration. The device material also may be tested directly on the patient’s skin to evaluate for hypersensitivity reactions. A test kit is sometimes available from the device manufacturer for this purpose; however, the provided test disks are not always adequate to prove a reaction. False-positive pressure effects and false-negative reactions may occur alongside irritant or other questionable reactions from the material (15,18,27).
Recommended Management for Device Placement in Patients with Nickel Allergy No evidence-based management recommendations exist; however, management routines have been proposed by various authors. Meier (11) suggested that nothing needs to be done before device implantation. In contrast, Thomas et al (28) described a German consensus to use titanium implants for all patients with metal allergy, and Lai et al (10) suggested a tapered oral dose of prednisone over 21 days for all patients with suspected metal allergy. In reviewing the previously proposed management regimens, Schalock et al (18) recommended a management algorithm. They proposed that no action is required if a patient with a positive patch test has no allergic symptoms after implant placement. If the patch test is positive and the patient is symptomatic after implant placement, the implant should be removed, as long as it is safe and feasible, and replaced with a nonallergenic alloy. However, if the implant cannot be removed, a 21-day tapered course of oral prednisone should be considered. Despite the varying opinions on management, most authors agree that a positive patch test and a positive history of nickel allergy should not automatically preclude a patient from receiving a medically needed metal device.
CONCLUSIONS The patient described in the present article had no adverse reaction to the nickel-containing IVC filter after placement for 36 days despite reported nickel contact
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dermatitis. No formal skin patch testing was performed to confirm her allergy. Nevertheless, despite the controversy in the literature regarding the relationship of nickel contact dermatitis and systemic response to nickel, most authors agree that nickel allergy is unlikely to be a true contraindication to placement of a nickelcontaining device. Lending support to this hypothesis is the finding that there are no reported incidents of nickel allergy to IVC filter placement to date despite the high prevalence of nickel allergy in the general population and large numbers of filters placed. Having reviewed the literature and given the rarity of reactions to endovascular devices, placing nickel-containing IVC filters as medically indicated in patients regardless of nickel allergy history does not appear to be contraindicated. Use of retrievable IVC filters in these patients is recommended because such filters potentially can be removed in the event of an allergic reaction, which appears to resolve symptoms in nearly all reported cases of allergic reaction to implantable metallic devices. Treating physicians may follow the recommended screening and treatment guidelines suggested by Schalock et al (18) before placement, but no scientific data support this screening, which is based on anecdotal recommendations. Evaluation of the incidence of nickel allergy with IVC filters and a more rigorous evaluation of the screening tools and their role in predicting allergic response to nickel-containing devices need to be performed. Creation of a prospective database for reporting allergic reactions and subsequent clinical course in patients with nickel allergy after IVC filter placement may be a first step toward elucidating the true effect of this phenomenon. In the present case, the patient was also driving the concern about her nickel allergies and whether the nickel-containing IVC filter would cause her problems. It is conceivable that other physicians may be aware of a nickel allergy in a patient needing an IVC filter who may be concerned about whether this is an issue with the current generation of devices. As physicians implanting such devices, the message to convey to patients is the relatively safe profile of inserting such devices as evidenced by the absence of documented problems despite so many insertions as well as the availability of retrievable options in the rare case of an allergic reaction.
REFERENCES 1. Schram SE, Warshaw EM, Laumann A. Nickel hypersensitivity: a clinical review and call to action. Int J Dermatol 2010; 49:115–125. 2. Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population—prevalence and main findings. Contact Dermatitis 2007; 57:287–299. 3. National Hospital Discharge Survey 1965-2010. Atlanta: Centers for Disease Control and Prevention; 2012. 4. Anselmino M, Ribezzo M, Orzan F. Nickel allergy, how deep? Acta Cardiol 2009; 64:104–106
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5. Arjona JE, Velasco E, Povedano B, Castillo R, Davalos S. Complications associated with the Essure device: analysis after 4000 procedures. Gynecol Surg 2010; 7:S89. 6. Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis 2011; 22:65–79. 7. Ekqvist S, Svedman C, Lundh T, Moller H, Bjork J, Bruze M. A correlation found between gold concentration in blood and patch test reactions in patients with coronary stents. Contact Dermatitis 2008; 59: 137–142. 8. Gimenez-Arnau A, Riambau V, Serra-Baldrich E, Camarasa JG. Metalinduced generalized pruriginous dermatitis and endovascular surgery. Contact Dermatitis 2000; 43:35–40. 9. Honari G, Ellis SG, Wilkoff BL, Aronica MA, Svensson LG, Taylor JS. Hypersensitivity reactions associated with endovascular devices. Contact Dermatitis 2008; 59:7–22. 10. Lai DW, Saver JL, Araujo JA, Reidl M, Tobis J. Pericarditis associated with nickel hypersensitivity to the Amplatzer occluder device: a case report. Catheter Cardiovasc Interv 2005; 66:424–426. 11. Meier B. Nickel allergy and device closure of the patent foramen ovale, now that we were told should we care? Catheter Cardiovasc Interv 2009; 74:652. 12. Povedano B, Arjona JE, Velasco E, Monserrat JA, Lorente J, CasteloBranco C. Complications of hysteroscopic Essure((R)) sterilisation: report on 4306 procedures performed in a single centre. BJOG 2012; 119:795–799. 13. Rabkin DG, Whitehead KJ, Michaels AD, Powell DL, Karwande SV. Unusual presentation of nickel allergy requiring explantation of an Amplatzer atrial septal occluder device. Clin Cardiol 2009; 32:E55–E57. 14. Reddy BT, Patel JB, Powell DL, Michaels AD. Interatrial shunt closure devices in patients with nickel allergy. Catheter Cardiovasc Interv 2009; 74:647–651. 15. Reed KB, Davis MD, Nakamura K, Hanson L, Richardson DM. Retrospective evaluation of patch testing before or after metal device implantation. Arch Dermatol 2008; 144:999–1007. 16. Ries MW, Kampmann C, Rupprecht HJ, Hintereder G, Hafner G, Meyer J. Nickel release after implantation of the Amplatzer occluder. Am Heart J 2003; 145:737–741. 17. Rigatelli G, Cardaioli P, Giordan M, et al. Nickel allergy in interatrial shunt device-based closure patients. Congenit Heart Dis 2007; 2: 416–420. 18. Schalock PC, Menne T, Johansen JD, et al. Hypersensitivity reactions to metallic implants—diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis 2012; 66:4–19. 19. Zurawin RK, Zurawin JL. Adverse events due to suspected nickel hypersensitivity in patients with essure micro-inserts. J Minim Invasive Gynecol 2011; 18:475–482. 20. Wang Y, Dai S. Structural basis of metal hypersensitivity. Immunol Res 2013; 55:83–90. 21. Messer RL, Wataha JC, Lewis JB, Lockwood PE, Caughman GB, Tseng WY. Effect of vascular stent alloys on expression of cellular adhesion molecules by endothelial cells. J Long Term Eff Med Implants 2005; 15: 39–47. 22. Templeton DM, Sunderman FW Jr, Herber RF. Tentative reference values for nickel concentrations in human serum, plasma, blood, and urine: evaluation according to the TRACY protocol. Sci Total Environ 1994; 148:243–251. 23. Nixon DE, Moyer TP, Squillace DP, McCarthy JT. Determination of serum nickel by graphite furnace atomic absorption spectrometry with Zeeman-effect background correction: values in a normal population and a population undergoing dialysis. Analyst 1989; 114:1671–1674. 24. Novelli EL, Rodrigues NL, Ribas BO. Superoxide radical and toxicity of environmental nickel exposure. Hum Exp Toxicol 1995; 14:248–251. 25. Wever DJ, Veldhuizen AG, de Vries J, Busscher HJ, Uges DR, van Horn JR. Electrochemical and surface characterization of a nickel-titanium alloy. Biomaterials 1998; 19:761–769. 26. Jetty P, Jayaram S, Veinot J, Pratt M. Superficial femoral artery nitinol stent in a patient with nickel allergy. J Vasc Surg 2013; 58:1388–1390. 27. de Fine Olivarius F, Menne T. Skin reactivity to metallic cobalt in patients with a positive patch test to cobalt chloride. Contact Dermatitis 1992; 27:241–243. 28. Thomas P, Schuh A, Ring J, Thomsen M. [Orthopedic surgical implants and allergies. Joint statement by the Implant Allergy Working Group (AK 20) of the DGOOC (German Association of Orthopedics and Orthopedic Surgery), DKG (German Contact Dermatitis Research Group) and DGAKI (German Society for Allergology and Clinical Immunology)]. Hautarzt 2008; 59:220–229.
