Correspondence
Severe Necrotizing Cutaneous Lesions Complicating Treatment with Interferon Beta-1b
N Engl J Med 1995; 332:1584-1585June 8, 1995
- Article
To the Editor:
Recombinant interferon beta-1b (Betaseron) was licensed in 1993 to reduce exacerbations of multiple sclerosis. Approval of the drug was greeted enthusiastically, despite a modest 30 percent reduction in relapses and side effects that include local inflammatory reactions and a flulike syndrome.1 We report the occurrence of severe necrotizing cutaneous reactions in a 38-year-old woman with an eight-year history of multiple sclerosis. She self-injected the standard dose of recombinant interferon beta-1b (9 million units) subcutaneously on alternate days.
Erythematous patches appeared at the injection sites on both thighs during the third month of treatment. These areas became violaceous, with a distinct livedoid pattern and black, necrotic ulcers measuring 2 by 2 cm to 2 by 4 cm at their centers (Figure 1AFigure 1
Severe Necrotizing Cutaneous Lesions in a Woman with Multiple Sclerosis Undergoing Treatment with Interferon Beta-1b.). Biopsy revealed marked acanthosis accompanied by superficial and deep perivascular and interstitial lymphocytic and histiocytic infiltrates mixed with neutrophils (Figure 1B). Deeper sections showed focal thrombosis of vessels. No evidence of systemic vasculitis was present.The areas healed after treatment with interferon beta-1b had been discontinued and therapy with interferon alfa-n3 (Alferon) was instituted. Although fever, fatigue, and prominent local reactions are common with interferon beta-1b, prominent skin necrosis seems to be a new complication.
Such severe reactions have not been reported with natural or recombinant interferon alfa,2,3 nor have we seen such reactions in our previous experience.4 Indeed, standard doses of interferon alfa (1 million units per milligram of protein) in 66 patients3,4 and of the highly purified, natural interferon alfa-n3 (100 million units per milligram) have been associated with remarkably few local skin reactions. Only one of the patients treated with interferon alfa-n3 had even a transient local flush. The adverse reactions to interferon beta-1b may not be inconsequential, and the use of natural interferon alfa in patients with multiple sclerosis requires further study.
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
The IFNB Multiple Sclerosis Study Group
Web of Science | Medline2
Knobler RL ,Panitch HS ,Braheny SL , et al. Systemic alpha-interferon of multiple sclerosis. Neurology 1984;34:1273-1279
Web of Science | Medline3
Durelli L ,Bongioanni MR ,Cavallo R , et al. Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 1994;44:406-413
Web of Science | Medline4
Sheremata WA ,Squillacote D ,Sazant A . Stabilization of relapsing-remitting and progressive multiple sclerosis with natural interferon-alpha: a preliminary trial. Ann Neurol 1994;32:327-327
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A. G. Beiske, K.-M. Myhr. (2006) Lipoatrophy: a non–reversible complication of subcutaneous interferon–beta 1a treatment of multiple sclerosis. Journal of Neurology 253:3, 377-378
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2006. Interferon beta. , 1831-1838.
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MG Ozden, A Erel, O Erdem, MO Oztas. (2005) Dermal fibrosis and cutaneous necrosis after recombinant interferon-beta1a injection in a multiple sclerosis patient. Journal of the European Academy of Dermatology and Venereology 19:1, 112-113
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Annarosa Virgili, Monica Corazza, Anna Rita Lombardi, Laura Sighinolfi. (1999) Cutaneous ulcers due to interferon seem not to be related to the dosage. Journal of the European Academy of Dermatology and Venereology 13:2, 141-143
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L Durelli, B Ferrero, A Oggero, E Verdun, M.R Bongioanni, E Gentile, G.L Isoardo, A Ricci, E Rota, B Bergamasco, M Durazzo, G Saracco, M.A Biava, P.C Brossa, L Giorda, R Pagni, G Aimo. (1999) Autoimmune events during interferon beta-1b treatment for multiple sclerosis. Journal of the Neurological Sciences 162:1, 74-83
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UTE KRAINICK, HAGOP KANTARJIAN, SHELA BROUSSARD, MOSHE TALPAZ. (1998) Local Cutaneous Necrotizing Lesions Associated with Interferon Injections. Journal of Interferon & Cytokine Research 18:10, 823-827
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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
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Frederick E. Munschauer, Revere Philip Kinkel. (1997) Managing side effects of interferon-beta in patients with relapsing-remitting multiple sclerosis. Clinical Therapeutics 19:5, 883-893
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Marco A. Maurtua, Lynn C. Moscinski, Jane Messina, Lisa Miller, Oscar F. Ballester. (1997) Type III hypersensitivity reaction with the use of interferon-α. American Journal of Hematology 55:1, 53-54
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M Azagury. (1996) Severe cutaneous reactions following interferon injections. European Journal of Cancer 32:10, 1821
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(1995) More on Interferon-Induced Cutaneous Necrosis. New England Journal of Medicine 333:18, 1222-1224
Full Text22
&NA;. (1995) Interferon-??-1b. Reactions Weekly &NA;:555, 8
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