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• W2031983886 abstract "To the Editor:I read with interest the article by Elgart et al entitled “Cutaneous Reactions to Recombinant Human Interferon beta-1b: The Clinical and Histologic Spectrum” (J Am Acad Dermatol 1997;37:553-8). We recently reviewed all cases of cutaneous necrosis associated with recombinant interferon (IFN) injection.1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar It is important to clarify that ulceration and findings of vascular thrombosis with interferon use are not restricted to IFN-β1b and patients with multiple sclerosis. Cnudde et al2Cnudde F Gharakhanian S Luboinski J Dry J Rozenbaum W. Cutaneous local necrosis following interferon injections.Int J Dermatol. 1991; 30 ([letter]): 147Crossref PubMed Scopus (62) Google Scholar first reported recombinant IFN-α-induced cutaneous necrosis at injection sites in a patient with AIDS-related Kaposi’s sarcoma (KS). Two months after treatment, this patient developed localized erythema, induration, and finally necrosis at the injection sites. A skin biopsy specimen revealed thrombotic occlusion of venules. The patient had a history of congenital type II antithrombin III deficiency but normal protein C and S levels. The authors theorized that local necrosis resulted from a procoagulant activity of IFN, possibly provoked or potentiated by the antithrombin III deficiency. Orlow and Friedman-Kien3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar subsequently described a similar case of cutaneous ulcerations at sites of repeated injections of IFN-α2b in a patient with KS. In an additional case involving IFN-α therapy,4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar a patient with AIDS-related KS developed atrophic plaques on the lower abdomen at the sites of IFN injection. Histologic examination showed that these lesions had necrotic changes within large venules deep in the dermis.In addition to the cases reported by Elgart et al, Berard et al5Berard F Canillot S Balme B Perrot H. Cutaneous local necrosis following interferon-beta injections.Ann Dermatol Venereol. 1995; 122: 105-107PubMed Google Scholar described a 56-year-old man in whom cutaneous necrosis developed at injection sites in the abdominal area after 6 months of treatment with IFN-β. A biopsy specimen revealed fibrin thrombosis of deep dermal vessels. There was no evidence of a coagulation abnormality in this patient. We also described 3 cases of ulceration caused by IFN-β injections in patients with multiple sclerosis. 1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar Biopsy was performed in only one case; there was no evidence of vascular thrombosis. In two of our cases, the patients were able to continue use of the IFN injections without further cutaneous ulceration.These cases of cutaneous ulceration in patients receiving interferon therapy suggest possible pathologic mechanisms. Most of the cases with documented histologic findings suggest that thrombosis and necrosis of dermal vessels are important etiologic factors. Such a local procoagulant effect may be caused by a toxic effect of the drug on the endothelium or a localized deficiency of an anticoagulant such as protein C. 4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar Orlow and Friedman-Kien 3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar attributed cutaneous ulceration to repeated injections in the same area. As in our first and second cases, this patient was able to continue injections in other skin sites without further complications. Most recently, Webster et al6Webster GF Knobler RL Lublin FD Kramer EM Hochman LR. Cutaneous ulcerations and pustular psoriasis caused by recombinant interferon beta injections.J Am Acad Dermatol. 1996; 34: 365-367Abstract Full Text PDF PubMed Google Scholar hypothesized that production of endogenous mediators or coadministered medications may create situations promoting ulceration or that there may be a vasospastic effect of the drug. They reported 1 patient who continued to use the IFN in whom the ulcerations ceased. Therefore they stated that the conditions favoring ulceration may be transitory.Additional cases will provide more information on the pathogenesis of cutaneous necrosis occurring after IFN therapy. Biopsy data will be helpful in elucidating mechanisms and may help to define subsets of cutaneous necrosis. In particular, it may be possible to define groups of patients in whom the therapy must be discontinued. This latter group may include those who are predisposed to local thrombosis of dermal vessels as a result of an inherited or acquired coagulopathy and therefore will not be able to tolerate treatment. To the Editor:I read with interest the article by Elgart et al entitled “Cutaneous Reactions to Recombinant Human Interferon beta-1b: The Clinical and Histologic Spectrum” (J Am Acad Dermatol 1997;37:553-8). We recently reviewed all cases of cutaneous necrosis associated with recombinant interferon (IFN) injection.1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar It is important to clarify that ulceration and findings of vascular thrombosis with interferon use are not restricted to IFN-β1b and patients with multiple sclerosis. Cnudde et al2Cnudde F Gharakhanian S Luboinski J Dry J Rozenbaum W. Cutaneous local necrosis following interferon injections.Int J Dermatol. 1991; 30 ([letter]): 147Crossref PubMed Scopus (62) Google Scholar first reported recombinant IFN-α-induced cutaneous necrosis at injection sites in a patient with AIDS-related Kaposi’s sarcoma (KS). Two months after treatment, this patient developed localized erythema, induration, and finally necrosis at the injection sites. A skin biopsy specimen revealed thrombotic occlusion of venules. The patient had a history of congenital type II antithrombin III deficiency but normal protein C and S levels. The authors theorized that local necrosis resulted from a procoagulant activity of IFN, possibly provoked or potentiated by the antithrombin III deficiency. Orlow and Friedman-Kien3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar subsequently described a similar case of cutaneous ulcerations at sites of repeated injections of IFN-α2b in a patient with KS. In an additional case involving IFN-α therapy,4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar a patient with AIDS-related KS developed atrophic plaques on the lower abdomen at the sites of IFN injection. Histologic examination showed that these lesions had necrotic changes within large venules deep in the dermis.In addition to the cases reported by Elgart et al, Berard et al5Berard F Canillot S Balme B Perrot H. Cutaneous local necrosis following interferon-beta injections.Ann Dermatol Venereol. 1995; 122: 105-107PubMed Google Scholar described a 56-year-old man in whom cutaneous necrosis developed at injection sites in the abdominal area after 6 months of treatment with IFN-β. A biopsy specimen revealed fibrin thrombosis of deep dermal vessels. There was no evidence of a coagulation abnormality in this patient. We also described 3 cases of ulceration caused by IFN-β injections in patients with multiple sclerosis. 1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar Biopsy was performed in only one case; there was no evidence of vascular thrombosis. In two of our cases, the patients were able to continue use of the IFN injections without further cutaneous ulceration.These cases of cutaneous ulceration in patients receiving interferon therapy suggest possible pathologic mechanisms. Most of the cases with documented histologic findings suggest that thrombosis and necrosis of dermal vessels are important etiologic factors. Such a local procoagulant effect may be caused by a toxic effect of the drug on the endothelium or a localized deficiency of an anticoagulant such as protein C. 4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar Orlow and Friedman-Kien 3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar attributed cutaneous ulceration to repeated injections in the same area. As in our first and second cases, this patient was able to continue injections in other skin sites without further complications. Most recently, Webster et al6Webster GF Knobler RL Lublin FD Kramer EM Hochman LR. Cutaneous ulcerations and pustular psoriasis caused by recombinant interferon beta injections.J Am Acad Dermatol. 1996; 34: 365-367Abstract Full Text PDF PubMed Google Scholar hypothesized that production of endogenous mediators or coadministered medications may create situations promoting ulceration or that there may be a vasospastic effect of the drug. They reported 1 patient who continued to use the IFN in whom the ulcerations ceased. Therefore they stated that the conditions favoring ulceration may be transitory.Additional cases will provide more information on the pathogenesis of cutaneous necrosis occurring after IFN therapy. Biopsy data will be helpful in elucidating mechanisms and may help to define subsets of cutaneous necrosis. In particular, it may be possible to define groups of patients in whom the therapy must be discontinued. This latter group may include those who are predisposed to local thrombosis of dermal vessels as a result of an inherited or acquired coagulopathy and therefore will not be able to tolerate treatment. I read with interest the article by Elgart et al entitled “Cutaneous Reactions to Recombinant Human Interferon beta-1b: The Clinical and Histologic Spectrum” (J Am Acad Dermatol 1997;37:553-8). We recently reviewed all cases of cutaneous necrosis associated with recombinant interferon (IFN) injection.1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar It is important to clarify that ulceration and findings of vascular thrombosis with interferon use are not restricted to IFN-β1b and patients with multiple sclerosis. Cnudde et al2Cnudde F Gharakhanian S Luboinski J Dry J Rozenbaum W. Cutaneous local necrosis following interferon injections.Int J Dermatol. 1991; 30 ([letter]): 147Crossref PubMed Scopus (62) Google Scholar first reported recombinant IFN-α-induced cutaneous necrosis at injection sites in a patient with AIDS-related Kaposi’s sarcoma (KS). Two months after treatment, this patient developed localized erythema, induration, and finally necrosis at the injection sites. A skin biopsy specimen revealed thrombotic occlusion of venules. The patient had a history of congenital type II antithrombin III deficiency but normal protein C and S levels. The authors theorized that local necrosis resulted from a procoagulant activity of IFN, possibly provoked or potentiated by the antithrombin III deficiency. Orlow and Friedman-Kien3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar subsequently described a similar case of cutaneous ulcerations at sites of repeated injections of IFN-α2b in a patient with KS. In an additional case involving IFN-α therapy,4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar a patient with AIDS-related KS developed atrophic plaques on the lower abdomen at the sites of IFN injection. Histologic examination showed that these lesions had necrotic changes within large venules deep in the dermis. In addition to the cases reported by Elgart et al, Berard et al5Berard F Canillot S Balme B Perrot H. Cutaneous local necrosis following interferon-beta injections.Ann Dermatol Venereol. 1995; 122: 105-107PubMed Google Scholar described a 56-year-old man in whom cutaneous necrosis developed at injection sites in the abdominal area after 6 months of treatment with IFN-β. A biopsy specimen revealed fibrin thrombosis of deep dermal vessels. There was no evidence of a coagulation abnormality in this patient. We also described 3 cases of ulceration caused by IFN-β injections in patients with multiple sclerosis. 1Weinberg JM Wolfe JT Sood S Saruk M Rook AH Spiers EM. Cutaneous necrosis associated with recombinant interferon injection: report of three cases with interferon beta-1b and review of the literature.Acta Derm Venereol (Stockh). 1997; 77: 146-148PubMed Google Scholar Biopsy was performed in only one case; there was no evidence of vascular thrombosis. In two of our cases, the patients were able to continue use of the IFN injections without further cutaneous ulceration. These cases of cutaneous ulceration in patients receiving interferon therapy suggest possible pathologic mechanisms. Most of the cases with documented histologic findings suggest that thrombosis and necrosis of dermal vessels are important etiologic factors. Such a local procoagulant effect may be caused by a toxic effect of the drug on the endothelium or a localized deficiency of an anticoagulant such as protein C. 4Oeda E Shinohara K. Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia.Am J Hematol. 1993; 44 ([letter]): 213-214Crossref PubMed Scopus (35) Google Scholar Orlow and Friedman-Kien 3Orlow SJ Friedman-Kien AE. Cutaneous ulceration secondary to interferon alfa therapy of Kaposi’s sarcoma.Arch Dermatol. 1992; 128 ([letter]): 566Crossref PubMed Scopus (42) Google Scholar attributed cutaneous ulceration to repeated injections in the same area. As in our first and second cases, this patient was able to continue injections in other skin sites without further complications. Most recently, Webster et al6Webster GF Knobler RL Lublin FD Kramer EM Hochman LR. Cutaneous ulcerations and pustular psoriasis caused by recombinant interferon beta injections.J Am Acad Dermatol. 1996; 34: 365-367Abstract Full Text PDF PubMed Google Scholar hypothesized that production of endogenous mediators or coadministered medications may create situations promoting ulceration or that there may be a vasospastic effect of the drug. They reported 1 patient who continued to use the IFN in whom the ulcerations ceased. Therefore they stated that the conditions favoring ulceration may be transitory. Additional cases will provide more information on the pathogenesis of cutaneous necrosis occurring after IFN therapy. Biopsy data will be helpful in elucidating mechanisms and may help to define subsets of cutaneous necrosis. In particular, it may be possible to define groups of patients in whom the therapy must be discontinued. This latter group may include those who are predisposed to local thrombosis of dermal vessels as a result of an inherited or acquired coagulopathy and therefore will not be able to tolerate treatment." @default.
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