Correspondence
More on Interferon-Induced Cutaneous Necrosis
N Engl J Med 1995; 333:1222-1224November 2, 1995
- Article
To the Editor:
Sheremata et al. (June 8 issue)1 reported severe necrotizing cutaneous lesions complicating treatment with interferon beta-1b in a patient with multiple sclerosis. They indicated that it was a new complication of treatment with interferon beta-1b, which had not been observed with natural or recombinant interferon alfa. However, we described a case of cutaneous necrosis caused by the injection of interferon alfa in a patient with chronic myelogenous leukemia.2 Cutaneous necrosis due to interferon alfa was also reported by Cnudde et al.3 and subsequently by Orlow and Friedman-Kien4 in patients with Kaposi's sarcoma related to the acquired immunodeficiency syndrome. The pathogenesis of cutaneous necrosis due to interferon alfa is unknown. A local immune-mediated inflammatory process in the skin may be involved.5
5 ReferencesKenji Shinohara, M.D.
Yamaguchi Prefecture, Central Hospital, Hofu 747, Japan1
Sheremata WA ,Taylor JR ,Elgart GW . Severe necrotizing cutaneous lesions complicating treatment with interferon beta-1b. N Engl J Med 1995;332:1584-1584
Full Text | Web of Science | Medline2
Oeda E ,Shinohara K . Cutaneous necrosis caused by injection of α-interferon in a patient with chronic myelogenous leukemia. Am J Hematol 1993;44:213-214
CrossRef | Web of Science | Medline3
Cnudde F ,Gharakhanian S ,Luboinski J ,Dry J ,Rozenbaum W . Cutaneous local necrosis following interferon injections. Int J Dermatol 1991;30:147-147
CrossRef | Web of Science | Medline4
Orlow SJ ,Friedman-Kien AE . Cutaneous ulcerations secondary to interferon alfa therapy of Kaposi's sarcoma. Arch Dermatol 1992;128:566-566
CrossRef | Web of Science | Medline5
Conlon KC ,Urba WJ ,Smith JW II ,Steis RG ,Longo DL ,Clark JW . Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 1990;65:2237-2242
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To the Editor:
Sheremata et al. report severe necrotizing lesions after subcutaneous injection of recombinant interferon beta-1b for the treatment of multiple sclerosis. They further report that the lesions healed after treatment with interferon beta-1b was discontinued and therapy with interferon alfa-n3 was instituted. As a rationale for changing the type of interferon used, the authors stated that necrotizing skin lesions had not been reported with natural or recombinant interferon alfa.
However, in 1989 Rasokat et al. described two cases of aseptic necrosis of the skin after subcutaneous self-injection of recombinant interferon alfa in patients with Kaposi's sarcoma associated with human immunodeficiency virus (HIV) infection.1 Although the exact mechanisms involved are unclear, the commonly accepted explanation is unintentional periarterial or intraarterial injection, with subsequent cutaneous infarction.2
2 ReferencesFranz Trautinger, M.D.
Robert M. Knobler, M.D.
University of Vienna Medical School, A-1090 Vienna, Austria1
Rasokat H ,Bendick C ,Wemmer U ,Steigleder GK . Aseptische Hautnekrose nach subkutaner Injektion von Interferon-α. Dtsch Med Wochenschr 1989;114:458-460
CrossRef | Web of Science | Medline2
Drug eruptions. In: Braun-Falco O, Plewig G, Wolff HH, Winkelmann RK. Dermatology. 3rd ed. Berlin, Germany: Springer-Verlag, 1991:289-90.
Author/Editor Response
The authors reply:
To the Editor: We thank Dr. Shinohara for bringing to our attention reports of cutaneous ulceration in recipients of interferon alfa that eluded our search of the literature. He and Oeda described a patient with chronic myelogenous leukemia and a cutaneous ulcer after injections of Japanese human interferon alfa of unstated specific activity.1 He also cites reports of two cases of ulceration complicating Kaposi's sarcoma associated with HIV infection and interferon alfa therapy,2,3 one of which was treated with both interferon alfa-2a and alfa-2b,2 and the other with interferon alfa-2b alone.3 Trautinger and Knobler cite a report of two cases of aseptic necrosis of the skin complicating Kaposi's sarcoma and HIV infection treated with an investigational German recombinant form of interferon alfa-1.4 However, such cutaneous ulceration must be rare with approved natural or recombinant interferon alfa, since we have seen no cases among our interferon alfa-2b–treated population, which includes more than 500 patients with hematologic disease, hepatitis B, or hepatitis C in addition to a considerable number of patients with HIV and Kaposi's sarcoma.
Recently, however, we examined a 40-year-old woman with multiple sclerosis who had two cutaneous ulcers at sites injected repeatedly with interferon alfa-2b (Figure 1AFigure 1
Cutaneous Ulcer in a Woman with Multiple Sclerosis Treated with Interferon Alfa-2b.). The histologic changes resembled those we reported with interferon beta-1b, including capillary and venous thrombosis but no arterial or arteriolar thrombosis (Figure 1B). Intraarterial injection, therefore, could not explain these vascular findings, as suggested by Trautinger and Knobler. However, the patient described by Cnudde et al. had a congenital type II antithrombin III deficiency, which is known to create a hypercoagulable state predisposing patients to venous thrombosis.2 Our continuing investigations of additional cases of ulceration complicating injections with interferon beta-1b for multiple sclerosis do not implicate antithrombin III deficiency as a cause but rather suggest the presence of unrelated preexisting factors that contribute to a hypercoagulable state in some patients, which may increase the risk of ulceration. Unlike the case with multiple sclerosis, cutaneous lesions occur without interferon therapy in chronic myelogenous leukemia and HIV infection, and multiple factors must be considered in the pathogenesis of ulceration complicating therapy with interferon alfa and other drugs.4 ReferencesWilliam A. Sheremata, M.D.
J. Richard Taylor, M.D.
George W. Elgart, M.D.
University of Miami School of Medicine, Miami, FL 331011
Oeda E ,Shinohara K . Cutaneous necrosis caused by injection of α-interferon in a patient with chronic myelogenous leukemia. Am J Hematol 1993;44:213-214
CrossRef | Web of Science | Medline2
Cnudde F ,Gharakhanian S ,Luboinski J ,Dry J ,Rozenbaum W . Cutaneous local necrosis following interferon injections. Int J Dermatol 1991;30:147-147
CrossRef | Web of Science | Medline3
Orlow SJ ,Friedman-Kien AE . Cutaneous ulcerations secondary to interferon alfa therapy of Kaposi's sarcoma. Arch Dermatol 1992;128:566-566
CrossRef | Web of Science | Medline4
Rasokat H ,Bendick C ,Wemmer U ,Steigleder GK . Aseptische Hautnekrose nach subkutaner Injektion von Interferon-α. Dtsch Med Wochenschr 1989;114:458-460
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
María Castellanos González, Mercedes Pérez Carreras, Raquel Muñoz Gómez, Gregorio Castellano Tortajada. (2011) Necrosis cutánea por interferón pegilado α-2b durante el tratamiento de la infección por el virus de la hepatitis C. Gastroenterología y Hepatología 34:8, 584-585
CrossRef2
Yun Jong Lee, Seong Wook Kang, Ju Kyoung Song, Han Joo Baek, Hyo Jin Choi, Young Deok Bae, Hee Jung Ryu, Eun Young Lee, Eun Bong Lee, Yeong Wook Song. (2007) Associations between interferon regulatory factor–1 polymorphisms and Behçet’s disease. Human Immunology 68:9, 770-778
CrossRef3
Sara K. Ward, Henry H. Roenigk, Kenneth B. Gordon. (1998) DERMATOLOGIC MANIFESTATIONS OF GASTROINTESTINAL DISORDERS. Gastroenterology Clinics of North America 27:3, 615-636
CrossRef4
J. B. Sickler, R. A. Simmons, D. K. Cobb, K. E. Sherman. (1998) Cutaneous Necrosis Associated With Interferon alpha-2b. The American Journal of Gastroenterology 93:3, 463-464
CrossRef
