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Cutaneous adverse events associated with long-term immunomodulating therapy in multiple sclerosis


Multiple sclerosis (MS) is a common immune-mediated inflammatory disease of the central nervous system that causes severe neurological disability [1]. Treatment is aimed at reducing disease progression via modulation of the immune system with disease-modifying therapies (DMTs) such as glatiramer acetate (GA) and interferon beta (IFN beta) [2]. Skin reactions to DMT are common and involve localized inflammatory processes [3].


Our aim was to assess the prevalence and type of cutaneous adverse events associated with long-term use of DMT.


A cross-sectional study was conducted in 2010-2011 among 15 clinics in the Netherlands. Eligible for inclusion were MS patients who were treated with their first DMT for at least 2 years. All consecutive eligible patients willing to participate were enrolled, irrespective of the presence of skin reactions. Skin reactions were assessed from digital photographs of the injection-sites by dermatologists, who were blinded for the DMT.


A total of 146 patients were enrolled. The median age was 47 years (interquartile range [IQR] 41-54 years) and most patients (76%) were female. The median duration of DMT treatment was 4 years (IQR 3-8). Forty-four (30%) patients were treated with intramuscular (IM) IFN beta-1a, 43 (29%) with subcutaneous (SC) IFN beta-1a, 38 (26%) with IFN beta-1b, and 21 (14%) with GA. The proportion of patients with cutaneous adverse events was 40%, 77%, 63%, and 81% among patients receiving IM IFN beta-1a, SC IFN beta-1a, SC IFN beta-1b, and GA, respectively. Skin reactions were local injection-site reactions (61%), lipoatrophy (24%), healed skin ulcers (7%), postinflammatory hyperpigmentation (4%), urticaria (3%), and skin necrosis (1%).


The prevalence of cutaneous adverse events associated with DMT treatment was high. The most common skin reactions were local injection-site reactions and lipoatrophy related to panniculitis.


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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Balak, D.M., Hengstman, G.J., Hupperts, R. et al. Cutaneous adverse events associated with long-term immunomodulating therapy in multiple sclerosis. J Transl Med 9 (Suppl 2), P14 (2011).

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