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Allergy in coronary in-stent restenosis
CORRESPONDENCE
5
endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells. J Invest Dermatol 1993; 100: 759–65. Milavec-Puretic V, Orlic D, Marusic A. Sensitivity to metals in 40 patients with failed hip endoprosthesis. Arch Orthop Trauma Surg 1998; 117: 383–86.
Sir—Ralf Köster and colleagues’1 proposed mechanism of nickel and molybdenum contact allergies being of importance in patients with coronary in-stent restenosis is intriguing. However, they include no information on the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The control of hypercholesterolaemia is crucial in the prevention of coronary-stent restenosis. Statin therapy can lower restenosis rates and improve clinical outcome after coronary stent implantation.2 Although Köster and colleagues tell us that the distribution of major risk factors for restenosis did not differ between patients with positive and negative patch-test results, the data in table 2 clearly show that only 40% of patients with positive patch tests had hypercholesterolaemia, compared with 71% in the negative patch test group. Hypercholesterolaemia (or an associated factor) could, therefore, be a confounding factor in this study. Specifically, we are concerned that hypercholesterolaemia treatment could have differed in the two groups. HMG-CoA-reductase inhibitors or statins are widely used after coronary-artery-stent implantation. Statins can directly inhibit expression of major histocompatibility complex (MHC)-II by interferon gamma and repress HMC-II-mediated T-cell activation.3 A dose-dependent effect has been seen in antigen-presenting cells, human endothelial cells, monocyte macrophages, and human smooth-muscle cells and fibroblasts. If statins do have substantial in-vivo immunosuppressive effects on coronary arteries, the fibroproliferationdescribed and inflammation-described in-stent restenoses will be affected. Patients on statins are less likely to restenose. In the skin, an allergen penetrating the skin classically associates with MHC-II molecules on antigen presenting cells. The use of statins before stenting could alter the induction of sensitivity to nickel or molybdenum. *T Ha, S Lalla Dermatology, Department of Medical and Radiological Sciences, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
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Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000; 356: 1895–97. Walter DH, Schachinger V, Elsner M, Mach S, Auch-Schwelk W, Zeiher AM. Effect of statin therapy on restenosis after coronary stent implantation. Am J Cardiol 2000; 85: 962–68. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognised type of immunomodulator. Nat Med 2000; 6: 1399–402.
Sir—Ralf Köster and colleagues1 do not discuss the behaviour of stainlesssteel grades in relation to nickel contact dermatitis. Haudrechy and colleagues2,3 showed that non-resulphurised stainless steels with a sulphur content of about 0·003% can be used without difficulty in long-term contact with skin. Stainless steels, however, with higher contents of sulphur, elicit nickel dermatitis in nickel-sensitised patients. The sulphur content of the stainless steel affects corrosion resistance and, thereby, release of nickel. We believe that the sulphur contents of the 316L stainless-steel stents used by Köster and colleagues should be measured. If, as we suspect, the stents have high sulphur content, replacement with implants that have low sulphur content might be better than avoidance of the use of stents in patients with known sensitisation to nickel, as Köster and colleagues suggest. *Daniel Mimouni, Akiva Trattner, Michael David *Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel; and Sackler Faculty of Medicine, Tel Aviv University 1
2
3
Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000; 356: 1895–97. Haudrechy P, Foussereau J, Mantout B, Baroux B. Nickel dermatitis from nickelplated metals and stainless steels. Contact Dermatitis 1994; 31: 249–55. Haudrechy P, Mantout B, Frappaz A, et al. Nickel release from stainless steels. Contact Dermatitis 1997; 37: 113–17.
Authors’ reply Sir—Fiona Keane and colleagues are surprised by the molybdenum allergy. They emphasise their comment with a reference from a study in which molybdenum caused no contact dermatitis in mice.1 However, hypersensitivity reactions to molybdenum are reported and it is identified as a sensitiser.1,2 Keane and colleagues state that guidance on salt to concentration in patch tests is limited. For this reason,
we followed the recommendations of the International Contact Dermatitis Research Group. We take note of their concern that we did not investigate patients who had no suspected restenosis. However, we do not believe that this additional cohort is essential to answer the questions of our study. We included an angiographically verified control group without restenosis. With this control cohort, an association of positive tests with or without restenosis can be detected. We agree that a prospective design might have been better to study the association between restenosis and hypersensitivity reaction. However, patients with nickel allergy are unlikely to agree to implantation of stainless steel stents, if carbon-coated stents with less metal ion release are available.3 The direct activation of endothelial cells by nickel chloride mentioned by Keane and colleagues is a different mechanism from the hypersensitivity reaction that we studied. However, their speculations about this as a factor for the development of in-stent restenosis seem plausible. We share Keane and colleagues’ opinion that many workers cannot answer whether nickel-containing prostheses should be avoided. In relation to whether our results are translatable into the clinical setting, we pointed out that the results are preliminary, mainly because of the number of patients. However, if these results are confirmed in a larger series of patients, possible benefits of carboncoated stents might be assessed in these patients. In answer to Ha and Lalla’s comment about the distribution of hypercholesterolaemia in the study cohorts, the difference in the frequency of hypercholesterolaemia and in the treatment with statins between the groups was not significant. Therefore, cholesterol-related and statin-related effects, such as they describe might not have greatly altered our results. Daniel Mimouni and colleagues suspect that the 316L steel stents in our study had high sulphur content. We did not measure sulphur content, because 316L has a defined low-sulphur composition. Accordingly, in the studies they cite, 316L steel was listed among the grades of stainless steel with low sulphur content. We have no reason to believe that the steel used for stents should vary from this defined 316L composition. *Ralf Köster, Dieter Vieluf, Marget Kiehn, Jan Kähler, Christian W Hamm Departments of *Cardiology and Dermatology, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
THE LANCET • Vol 357 • April 14, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
5
endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells. J Invest Dermatol 1993; 100: 759–65. Milavec-Puretic V, Orlic D, Marusic A. Sensitivity to metals in 40 patients with failed hip endoprosthesis. Arch Orthop Trauma Surg 1998; 117: 383–86.
Sir—Ralf Köster and colleagues’1 proposed mechanism of nickel and molybdenum contact allergies being of importance in patients with coronary in-stent restenosis is intriguing. However, they include no information on the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The control of hypercholesterolaemia is crucial in the prevention of coronary-stent restenosis. Statin therapy can lower restenosis rates and improve clinical outcome after coronary stent implantation.2 Although Köster and colleagues tell us that the distribution of major risk factors for restenosis did not differ between patients with positive and negative patch-test results, the data in table 2 clearly show that only 40% of patients with positive patch tests had hypercholesterolaemia, compared with 71% in the negative patch test group. Hypercholesterolaemia (or an associated factor) could, therefore, be a confounding factor in this study. Specifically, we are concerned that hypercholesterolaemia treatment could have differed in the two groups. HMG-CoA-reductase inhibitors or statins are widely used after coronary-artery-stent implantation. Statins can directly inhibit expression of major histocompatibility complex (MHC)-II by interferon gamma and repress HMC-II-mediated T-cell activation.3 A dose-dependent effect has been seen in antigen-presenting cells, human endothelial cells, monocyte macrophages, and human smooth-muscle cells and fibroblasts. If statins do have substantial in-vivo immunosuppressive effects on coronary arteries, the fibroproliferationdescribed and inflammation-described in-stent restenoses will be affected. Patients on statins are less likely to restenose. In the skin, an allergen penetrating the skin classically associates with MHC-II molecules on antigen presenting cells. The use of statins before stenting could alter the induction of sensitivity to nickel or molybdenum. *T Ha, S Lalla Dermatology, Department of Medical and Radiological Sciences, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
1206
I
2
3
Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000; 356: 1895–97. Walter DH, Schachinger V, Elsner M, Mach S, Auch-Schwelk W, Zeiher AM. Effect of statin therapy on restenosis after coronary stent implantation. Am J Cardiol 2000; 85: 962–68. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognised type of immunomodulator. Nat Med 2000; 6: 1399–402.
Sir—Ralf Köster and colleagues1 do not discuss the behaviour of stainlesssteel grades in relation to nickel contact dermatitis. Haudrechy and colleagues2,3 showed that non-resulphurised stainless steels with a sulphur content of about 0·003% can be used without difficulty in long-term contact with skin. Stainless steels, however, with higher contents of sulphur, elicit nickel dermatitis in nickel-sensitised patients. The sulphur content of the stainless steel affects corrosion resistance and, thereby, release of nickel. We believe that the sulphur contents of the 316L stainless-steel stents used by Köster and colleagues should be measured. If, as we suspect, the stents have high sulphur content, replacement with implants that have low sulphur content might be better than avoidance of the use of stents in patients with known sensitisation to nickel, as Köster and colleagues suggest. *Daniel Mimouni, Akiva Trattner, Michael David *Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel; and Sackler Faculty of Medicine, Tel Aviv University 1
2
3
Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000; 356: 1895–97. Haudrechy P, Foussereau J, Mantout B, Baroux B. Nickel dermatitis from nickelplated metals and stainless steels. Contact Dermatitis 1994; 31: 249–55. Haudrechy P, Mantout B, Frappaz A, et al. Nickel release from stainless steels. Contact Dermatitis 1997; 37: 113–17.
Authors’ reply Sir—Fiona Keane and colleagues are surprised by the molybdenum allergy. They emphasise their comment with a reference from a study in which molybdenum caused no contact dermatitis in mice.1 However, hypersensitivity reactions to molybdenum are reported and it is identified as a sensitiser.1,2 Keane and colleagues state that guidance on salt to concentration in patch tests is limited. For this reason,
we followed the recommendations of the International Contact Dermatitis Research Group. We take note of their concern that we did not investigate patients who had no suspected restenosis. However, we do not believe that this additional cohort is essential to answer the questions of our study. We included an angiographically verified control group without restenosis. With this control cohort, an association of positive tests with or without restenosis can be detected. We agree that a prospective design might have been better to study the association between restenosis and hypersensitivity reaction. However, patients with nickel allergy are unlikely to agree to implantation of stainless steel stents, if carbon-coated stents with less metal ion release are available.3 The direct activation of endothelial cells by nickel chloride mentioned by Keane and colleagues is a different mechanism from the hypersensitivity reaction that we studied. However, their speculations about this as a factor for the development of in-stent restenosis seem plausible. We share Keane and colleagues’ opinion that many workers cannot answer whether nickel-containing prostheses should be avoided. In relation to whether our results are translatable into the clinical setting, we pointed out that the results are preliminary, mainly because of the number of patients. However, if these results are confirmed in a larger series of patients, possible benefits of carboncoated stents might be assessed in these patients. In answer to Ha and Lalla’s comment about the distribution of hypercholesterolaemia in the study cohorts, the difference in the frequency of hypercholesterolaemia and in the treatment with statins between the groups was not significant. Therefore, cholesterol-related and statin-related effects, such as they describe might not have greatly altered our results. Daniel Mimouni and colleagues suspect that the 316L steel stents in our study had high sulphur content. We did not measure sulphur content, because 316L has a defined low-sulphur composition. Accordingly, in the studies they cite, 316L steel was listed among the grades of stainless steel with low sulphur content. We have no reason to believe that the steel used for stents should vary from this defined 316L composition. *Ralf Köster, Dieter Vieluf, Marget Kiehn, Jan Kähler, Christian W Hamm Departments of *Cardiology and Dermatology, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
THE LANCET • Vol 357 • April 14, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.