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Allergic Reaction following Implantation of a Nitinol Alloy Inferior Vena Cava Filter
BRIEF REPORT
Allergic Reaction following Implantation of a Nitinol Alloy Inferior Vena Cava Filter Zhongzhi Jia, MD, JianFei Tu, MD, Kai Wang, MD, Guomin Jiang, MD, and Weiping Wang, MD ABSTRACT A 67-year-old woman developed severe pruritus after implantation of a retrievable nitinol inferior vena cava (IVC) filter (55.4% nickel and 44.6% titanium). The pruritus resolved only after filter retrieval. The patient’s hypersensitivity to nickel was confirmed by a positive skin patch test substantiating a systemic allergic reaction to the implanted nitinol IVC filter. ABBREVIATION IVC = inferior vena cava
An inferior vena cava (IVC) filter is a small metal device that is implanted in the IVC to prevent migration of lower extremity deep venous thrombosis to the lungs, a potential life-threatening condition. The use of an IVC filter is generally regarded as safe; however, complications related to the device itself can occur, such as filter fracture, migration, misplacement, and caval penetration (1–3). In August 2010, the US Food and Drug Administration released an initial communication on the risk and adverse events associated with long-term use of an IVC filter (4). Allergic reaction to the nitinol filter as a complication related to the device is extremely rare and can be clinically challenging in terms of diagnosis and subsequent management.
CASE REPORT The institutional review board approved this study, and informed consent was obtained from the patient. A 67year-old woman presented with acute-onset left lower extremity severe swelling associated with pain that had begun days previously. Ascending venography of From the Department of Interventional Radiology (Z.J., K.W., G.J.), No. 2 People’s Hospital of Changzhou, Nanjing Medical University, Xing Long Road 29#, Chang Zhou, Jiangsu Province 213003, China; Department of Radiology and Interventional Radiology (J.T.), Li Shui Central Hospital, Li Shui, Zhejiang Province, China; and Department of Radiology (W.W.), Mayo Clinic, Jacksonville, Florida. Received March 25, 2015; final revision received and accepted May 30, 2015. Address correspondence to G.J.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2015 J Vasc Interv Radiol 2015; 26:1375–1377 http://dx.doi.org/10.1016/j.jvir.2015.05.033
the left lower extremity demonstrated extensive diffuse intraluminal filling defects from the calf to the iliofemoral veins. In addition, an iliofemoral thrombosis appeared to be free-floating on ultrasound examination. The decision was made to perform endovascular thrombectomy because of the symptoms and extent of the disease. Because there was a risk that the free-floating thrombosis could migrate to the lungs, a retrievable IVC filter (Aegisy; Lifetech Scientific [Shenzhen] Co, Ltd, Shenzhen, China) (Figs 1, 2) was implanted in the infrarenal IVC by the right femoral vein before endovascular thrombectomy was performed. The thrombectomy procedure was performed with the aspiration technique. Antegrade access was obtained through the popliteal vein at the popliteal fossa. A 9-F guiding catheter was inserted, and the clots in the iliofemoral and femoral veins were removed. After thrombectomy, the patient received continuous urokinase (300,000 units per 12 h) infusion through the popliteal venous access, and intravenous heparin was switched to low-molecularweight heparin while the filter was in place. The patient developed severe pruritus all over her body 2 days after completion of the thrombectomy procedure. There was no skin rash or hives. The patient was a farmer and had no history of allergies. She was unaware of any history of exposure to heavy metals. An allergic reaction to urokinase or low-molecular-weight heparin was suspected. The patient’s white blood cell (7.2 109/L) and eosinophil (0.27 109/L) counts were within normal limits. Treatment with steroids and antihistamine agents was initiated (dexamethasone 5 mg/d and loratadine 10 mg once daily); additionally, the urokinase was discontinued immediately, and oral warfarin (Qilu Pharmaceutical Co, Ltd, Jinan, China) was
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Allergic Reaction of a Nitinol IVC Filter
Jia et al
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Figure 1. A retrievable IVC filter was implanted in the infrarenal IVC before endovascular thrombectomy was performed.
initiated. Dexamethasone and loratadine were discontinued 5 days after the procedure, and low-molecularweight heparin was withdrawn. However, the next day the patient complained of severe pruritus again. A hypersensitivity to the nickel-containing IVC filter or warfarin was suspected. The patient was referred to a specialist hospital with access to skin patch testing. The presence of a nickel allergy was confirmed, and the filter was retrieved. Venography performed before and after filter retrieval demonstrated no clot in the filter or other abnormal findings. Within hours of filter removal, the patient’s pruritus resolved without further steroid or antihistamine treatment. After filter removal, the patient underwent nickel hypersensitivity testing at a specialist hospital in our region and showed a positive reaction to nickel (skin rash). At a 3-month follow-up examination, there was no evidence of pruritus, skin hives, or rash.
DISCUSSION Nickel is the most common occupational and contact allergen, affecting approximately 8.6% of the population (5,6). The incidence of hypersensitivity to nickel may be 15% (7). Manufacturers warn that use of a nickelcontaining device can potentially cause an allergic reaction, although the incidence of such allergic reactions with these devices is extremely rare (8). According to the manufacturer, the filter used in our case is composed of 55.4% nickel and 44.6% titanium, which is higher in nickel content than most filters currently available in the United States.
Figure 2. The filter was retrieved, and there was no clot in the filter.
To the best of our knowledge, a reaction to a nitinolcontaining filter has not been previously reported. In a report by Morshedi and Kinney (9), there was no single case of hypersensitivity attributed to a nickel-containing IVC filter after extensive review of the literature and the Manufacturer and User Facility Device Experience database. Nevertheless, hypersensitivity to other nickelcontaining devices, such as the Essure sterilization device (Bayer HealthCare Pharmaceuticals, Inc, Whippany, New Jersey) (10), AMPLATZER occluder (St. Jude Medical, Inc, St. Paul, Minnesota) (8), vascular and nonvascular stents (11), and other endovascular and implantable devices (5), has been well documented in the literature. Jetty et al (11) postulated that the following factors may contribute to the low reported incidence of nickel hypersensitivity associated with
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nickel-containing IVC filters: (i) the amount of free nickel allergen from nitinol filters may be too low in most individuals to cause a clinically significant reaction, (ii) the intravascular location of the nickel exposure may dilute the severity of the reaction compared with a localized dermal exposure, and (iii) cases of pruritus after filter placement may not be recognized. The “nickel itch” is an early symptom of nickel hypersensitivity and is often followed by severe dermatitis, which can be continuous as long as the allergen is present (11). However, the patient in our case had severe pruritus only. Reported reactions at the site of metal implants include type IV reactions but are probably complex in nature. Peri-implant reactions seem to be Th1 dominant. Researchers found that there are increased levels of interferon-γ and interleukin-6 in metal-allergic patients with joint arthroplasties (12,13). Analyses of tissues adjacent to implanted metals in patients with metal hypersensitivity demonstrated elevated levels of immune cells/markers, including CD3þ T lymphocytes, CD4þ cells, CD11cþ macrophages/dendritic cells, and cells with abundant major histocompatibility complex class II (human leukocyte antigen-DR) expression (dendritic cells) (14). However, the mechanism of nickel allergy remains unknown. Most patients in these studies had a silent past medical history, and the symptoms of nickel hypersensitivity occurred only after the device was implanted. In such cases, the nickel skin patch test can be used to confirm the source of the hypersensitivity reaction. Nickel-containing IVC filters may be difficult to avoid because almost all filter manufacturers use alloys that contain nickel. In a patient with a known history of nickel hypersensitivity, a retrievable filter may be considered over a permanent one because the filter can be removed if an adverse reaction occurs. Patients with a known nickel allergy should also be informed about the low risk of an allergic reaction and should be told to seek medical advice if any concerning symptoms arise. However, patients with a history of nickel hypersensitivity would not necessarily have an adverse reaction to filter placement. Morshedi and Kinney (9) reported that a Günther Tulip retrievable IVC filter (Cook; Bloomington, Indiana) was placed in a patient with nickel hypersensitivity without complications. A nickel hypersensitivity may not be an absolute contraindication for the use of devices that contain nickel (15). In the present case, a nickel skin test was performed, but other components in the filter such as titanium were not tested. The clinical symptoms were completely resolved after filter removal, which may have been a coincidence, although this is unlikely. In conclusion, allergy to nickel-containing IVC filters is rare but can cause significant clinical symptoms. Permanent IVC filters should be avoided if there is a
1377
well-documented history of hypersensitivity to nickel. A positive nickel skin patch test can help to confirm the source of the reaction but may be unable to predict outcomes before the device is implanted. If an allergic reaction occurs after filter placement, the filter should be removed.
ACKNOWLEDGMENT The authors thank Matthew Tam, MD, Department of Radiology, Southend University Hospital, NHS Foundation Trust, Essex, United Kingdom, for his contribution to this manuscript, and Megan Griffiths, Imaging Institute, Cleveland, Ohio, for her help with revising the manuscript.
REFERENCES 1. Andreoli JM, Lewandowski RJ, Vogelzang RL, Ryu RK. Comparison of complication rates associated with permanent and retrievable inferior vena cava filters: a review of the MAUDE database. J Vasc Interv Radiol 2014; 25:1181–1185. 2. Wang W, Zhou D, Obuchowski N, Spain J, An T, Moon E. Fracture and migration of celect inferior vena cava filters: a retrospective review of 741 consecutive implantations. J Vasc Interv Radiol 2013; 24:1719–1722. 3. Angel LF, Tapson V, Galgon RE, Restrepo MI, Kaufman J. Systematic review of the use of retrievable inferior vena cava filters. J Vasc Interv Radiol 2011; 22:1522–1530.e1523. 4. United States Food and Drug Administration. Alerts and notices (medical devices). Removing retrievable inferior vena cava filters: initial communication. Issued August 9, 2010. Available at: http://www.fda.gov/Medical Devices/Safety/AlertsandNotices/ucm221676.htm. Accessed May 27, 2015. 5. Schram SE, Warshaw EM, Laumann A. Nickel hypersensitivity: a clinical review and call to action. Int J Dermatol 2010; 49:115–125. 6. 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. 7. Cohen DE. Contact dermatitis: a quarter century perspective. J Am Acad Dermatol 2004; 51(1 Suppl):S60–S63. 8. 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. 9. Morshedi MM, Kinney TB. Nickel hypersensitivity in patients with inferior vena cava filters: case report and literature and MAUDE database review. J Vasc Interv Radiol 2014; 25:1187–1191. 10. 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. 11. 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. 12. Hallab NJ, Caicedo M, Finnegan A, Jacobs JJ. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty. J Orthop Surg 2008; 3:6. 13. Thomas P, Summer B, Sander CA, Przybilla B, Thomas M, Naumann T. Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T-cell infiltrate and TH1-type cytokine expression in the peri-implantar tissue. Allergy 2000; 55:969–972. 14. Cadosch D, Chan E, Gautschi OP, Filgueira L. Metal is not inert: role of metal ions released by biocorrosion in aseptic loosening-current concepts. J Biomed Mater Res A 2009; 91:1252–1262. 15. Anselmino M, Ribezzo M, Orzan F. Nickel allergy, how deep? Acta Cardiol 2009; 64:104–106.
Allergic Reaction following Implantation of a Nitinol Alloy Inferior Vena Cava Filter Zhongzhi Jia, MD, JianFei Tu, MD, Kai Wang, MD, Guomin Jiang, MD, and Weiping Wang, MD ABSTRACT A 67-year-old woman developed severe pruritus after implantation of a retrievable nitinol inferior vena cava (IVC) filter (55.4% nickel and 44.6% titanium). The pruritus resolved only after filter retrieval. The patient’s hypersensitivity to nickel was confirmed by a positive skin patch test substantiating a systemic allergic reaction to the implanted nitinol IVC filter. ABBREVIATION IVC = inferior vena cava
An inferior vena cava (IVC) filter is a small metal device that is implanted in the IVC to prevent migration of lower extremity deep venous thrombosis to the lungs, a potential life-threatening condition. The use of an IVC filter is generally regarded as safe; however, complications related to the device itself can occur, such as filter fracture, migration, misplacement, and caval penetration (1–3). In August 2010, the US Food and Drug Administration released an initial communication on the risk and adverse events associated with long-term use of an IVC filter (4). Allergic reaction to the nitinol filter as a complication related to the device is extremely rare and can be clinically challenging in terms of diagnosis and subsequent management.
CASE REPORT The institutional review board approved this study, and informed consent was obtained from the patient. A 67year-old woman presented with acute-onset left lower extremity severe swelling associated with pain that had begun days previously. Ascending venography of From the Department of Interventional Radiology (Z.J., K.W., G.J.), No. 2 People’s Hospital of Changzhou, Nanjing Medical University, Xing Long Road 29#, Chang Zhou, Jiangsu Province 213003, China; Department of Radiology and Interventional Radiology (J.T.), Li Shui Central Hospital, Li Shui, Zhejiang Province, China; and Department of Radiology (W.W.), Mayo Clinic, Jacksonville, Florida. Received March 25, 2015; final revision received and accepted May 30, 2015. Address correspondence to G.J.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2015 J Vasc Interv Radiol 2015; 26:1375–1377 http://dx.doi.org/10.1016/j.jvir.2015.05.033
the left lower extremity demonstrated extensive diffuse intraluminal filling defects from the calf to the iliofemoral veins. In addition, an iliofemoral thrombosis appeared to be free-floating on ultrasound examination. The decision was made to perform endovascular thrombectomy because of the symptoms and extent of the disease. Because there was a risk that the free-floating thrombosis could migrate to the lungs, a retrievable IVC filter (Aegisy; Lifetech Scientific [Shenzhen] Co, Ltd, Shenzhen, China) (Figs 1, 2) was implanted in the infrarenal IVC by the right femoral vein before endovascular thrombectomy was performed. The thrombectomy procedure was performed with the aspiration technique. Antegrade access was obtained through the popliteal vein at the popliteal fossa. A 9-F guiding catheter was inserted, and the clots in the iliofemoral and femoral veins were removed. After thrombectomy, the patient received continuous urokinase (300,000 units per 12 h) infusion through the popliteal venous access, and intravenous heparin was switched to low-molecularweight heparin while the filter was in place. The patient developed severe pruritus all over her body 2 days after completion of the thrombectomy procedure. There was no skin rash or hives. The patient was a farmer and had no history of allergies. She was unaware of any history of exposure to heavy metals. An allergic reaction to urokinase or low-molecular-weight heparin was suspected. The patient’s white blood cell (7.2 109/L) and eosinophil (0.27 109/L) counts were within normal limits. Treatment with steroids and antihistamine agents was initiated (dexamethasone 5 mg/d and loratadine 10 mg once daily); additionally, the urokinase was discontinued immediately, and oral warfarin (Qilu Pharmaceutical Co, Ltd, Jinan, China) was
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Allergic Reaction of a Nitinol IVC Filter
Jia et al
’
JVIR
Figure 1. A retrievable IVC filter was implanted in the infrarenal IVC before endovascular thrombectomy was performed.
initiated. Dexamethasone and loratadine were discontinued 5 days after the procedure, and low-molecularweight heparin was withdrawn. However, the next day the patient complained of severe pruritus again. A hypersensitivity to the nickel-containing IVC filter or warfarin was suspected. The patient was referred to a specialist hospital with access to skin patch testing. The presence of a nickel allergy was confirmed, and the filter was retrieved. Venography performed before and after filter retrieval demonstrated no clot in the filter or other abnormal findings. Within hours of filter removal, the patient’s pruritus resolved without further steroid or antihistamine treatment. After filter removal, the patient underwent nickel hypersensitivity testing at a specialist hospital in our region and showed a positive reaction to nickel (skin rash). At a 3-month follow-up examination, there was no evidence of pruritus, skin hives, or rash.
DISCUSSION Nickel is the most common occupational and contact allergen, affecting approximately 8.6% of the population (5,6). The incidence of hypersensitivity to nickel may be 15% (7). Manufacturers warn that use of a nickelcontaining device can potentially cause an allergic reaction, although the incidence of such allergic reactions with these devices is extremely rare (8). According to the manufacturer, the filter used in our case is composed of 55.4% nickel and 44.6% titanium, which is higher in nickel content than most filters currently available in the United States.
Figure 2. The filter was retrieved, and there was no clot in the filter.
To the best of our knowledge, a reaction to a nitinolcontaining filter has not been previously reported. In a report by Morshedi and Kinney (9), there was no single case of hypersensitivity attributed to a nickel-containing IVC filter after extensive review of the literature and the Manufacturer and User Facility Device Experience database. Nevertheless, hypersensitivity to other nickelcontaining devices, such as the Essure sterilization device (Bayer HealthCare Pharmaceuticals, Inc, Whippany, New Jersey) (10), AMPLATZER occluder (St. Jude Medical, Inc, St. Paul, Minnesota) (8), vascular and nonvascular stents (11), and other endovascular and implantable devices (5), has been well documented in the literature. Jetty et al (11) postulated that the following factors may contribute to the low reported incidence of nickel hypersensitivity associated with
Volume 26
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Number 9
’
September
’
2015
nickel-containing IVC filters: (i) the amount of free nickel allergen from nitinol filters may be too low in most individuals to cause a clinically significant reaction, (ii) the intravascular location of the nickel exposure may dilute the severity of the reaction compared with a localized dermal exposure, and (iii) cases of pruritus after filter placement may not be recognized. The “nickel itch” is an early symptom of nickel hypersensitivity and is often followed by severe dermatitis, which can be continuous as long as the allergen is present (11). However, the patient in our case had severe pruritus only. Reported reactions at the site of metal implants include type IV reactions but are probably complex in nature. Peri-implant reactions seem to be Th1 dominant. Researchers found that there are increased levels of interferon-γ and interleukin-6 in metal-allergic patients with joint arthroplasties (12,13). Analyses of tissues adjacent to implanted metals in patients with metal hypersensitivity demonstrated elevated levels of immune cells/markers, including CD3þ T lymphocytes, CD4þ cells, CD11cþ macrophages/dendritic cells, and cells with abundant major histocompatibility complex class II (human leukocyte antigen-DR) expression (dendritic cells) (14). However, the mechanism of nickel allergy remains unknown. Most patients in these studies had a silent past medical history, and the symptoms of nickel hypersensitivity occurred only after the device was implanted. In such cases, the nickel skin patch test can be used to confirm the source of the hypersensitivity reaction. Nickel-containing IVC filters may be difficult to avoid because almost all filter manufacturers use alloys that contain nickel. In a patient with a known history of nickel hypersensitivity, a retrievable filter may be considered over a permanent one because the filter can be removed if an adverse reaction occurs. Patients with a known nickel allergy should also be informed about the low risk of an allergic reaction and should be told to seek medical advice if any concerning symptoms arise. However, patients with a history of nickel hypersensitivity would not necessarily have an adverse reaction to filter placement. Morshedi and Kinney (9) reported that a Günther Tulip retrievable IVC filter (Cook; Bloomington, Indiana) was placed in a patient with nickel hypersensitivity without complications. A nickel hypersensitivity may not be an absolute contraindication for the use of devices that contain nickel (15). In the present case, a nickel skin test was performed, but other components in the filter such as titanium were not tested. The clinical symptoms were completely resolved after filter removal, which may have been a coincidence, although this is unlikely. In conclusion, allergy to nickel-containing IVC filters is rare but can cause significant clinical symptoms. Permanent IVC filters should be avoided if there is a
1377
well-documented history of hypersensitivity to nickel. A positive nickel skin patch test can help to confirm the source of the reaction but may be unable to predict outcomes before the device is implanted. If an allergic reaction occurs after filter placement, the filter should be removed.
ACKNOWLEDGMENT The authors thank Matthew Tam, MD, Department of Radiology, Southend University Hospital, NHS Foundation Trust, Essex, United Kingdom, for his contribution to this manuscript, and Megan Griffiths, Imaging Institute, Cleveland, Ohio, for her help with revising the manuscript.
REFERENCES 1. Andreoli JM, Lewandowski RJ, Vogelzang RL, Ryu RK. Comparison of complication rates associated with permanent and retrievable inferior vena cava filters: a review of the MAUDE database. J Vasc Interv Radiol 2014; 25:1181–1185. 2. Wang W, Zhou D, Obuchowski N, Spain J, An T, Moon E. Fracture and migration of celect inferior vena cava filters: a retrospective review of 741 consecutive implantations. J Vasc Interv Radiol 2013; 24:1719–1722. 3. Angel LF, Tapson V, Galgon RE, Restrepo MI, Kaufman J. Systematic review of the use of retrievable inferior vena cava filters. J Vasc Interv Radiol 2011; 22:1522–1530.e1523. 4. United States Food and Drug Administration. Alerts and notices (medical devices). Removing retrievable inferior vena cava filters: initial communication. Issued August 9, 2010. Available at: http://www.fda.gov/Medical Devices/Safety/AlertsandNotices/ucm221676.htm. Accessed May 27, 2015. 5. Schram SE, Warshaw EM, Laumann A. Nickel hypersensitivity: a clinical review and call to action. Int J Dermatol 2010; 49:115–125. 6. 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. 7. Cohen DE. Contact dermatitis: a quarter century perspective. J Am Acad Dermatol 2004; 51(1 Suppl):S60–S63. 8. 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. 9. Morshedi MM, Kinney TB. Nickel hypersensitivity in patients with inferior vena cava filters: case report and literature and MAUDE database review. J Vasc Interv Radiol 2014; 25:1187–1191. 10. 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. 11. 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. 12. Hallab NJ, Caicedo M, Finnegan A, Jacobs JJ. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty. J Orthop Surg 2008; 3:6. 13. Thomas P, Summer B, Sander CA, Przybilla B, Thomas M, Naumann T. Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T-cell infiltrate and TH1-type cytokine expression in the peri-implantar tissue. Allergy 2000; 55:969–972. 14. Cadosch D, Chan E, Gautschi OP, Filgueira L. Metal is not inert: role of metal ions released by biocorrosion in aseptic loosening-current concepts. J Biomed Mater Res A 2009; 91:1252–1262. 15. Anselmino M, Ribezzo M, Orzan F. Nickel allergy, how deep? Acta Cardiol 2009; 64:104–106.