Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review

Abstract

<jats:p>Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT.</jats:p>

The heritage of glatiramer acetate and its use in multiple sclerosis

“…These include injection site bruising, erythema, pain, pruritus and induration. Rarer cases of localized lipoatrophy and skin necrosis at injection sites have been reported during post-marketing [111,112]. One peculiar injection-related tolerability issue with GA is the occurrence of immediate post-injection reactions (IPIR) that present immediately or a few minutes after the injection, consisting in flushing, chest tightness, palpitation, dyspnoea and intense anxiety.…”

Management Strategies for Flu-Like Symptoms and Injection-Site Reactions Associated with Peginterferon Beta-1a

“…5,6,9,16 Typically, FLSs occur within 6 hours after injection, dissipate within 24 hours, and are most prevalent during the first 6 months of treatment. 10,17,18 Consistent with this and based on the experiences in the ADVANCE study, the frequency and duration of FLSs generally declined after 3 months of treatment in a typical patient treated with peginterferon beta-1a.…”

Lipoatrophy After Pegylated Interferon Treatment for Chronic Hepatitis C Virus Infection

“…The main sources of information are studies in the field of neuroscience and the long-term follow-up of patients with multiple sclerosis receiving subcutaneous interferon. 1 Most of these studies provide evidence of the rather long latent period between treatment initiation and onset of lipoatrophy (mean, 2.5-3 years). 1 Limited reports of similar cases have also been reported in HCV patients, 2 whereas early onset of lipoatrophy has been reported only on rare occasions (within the time frame of the therapy or shortly after).…”

“…1 Most of these studies provide evidence of the rather long latent period between treatment initiation and onset of lipoatrophy (mean, 2.5-3 years). 1 Limited reports of similar cases have also been reported in HCV patients, 2 whereas early onset of lipoatrophy has been reported only on rare occasions (within the time frame of the therapy or shortly after). 3 Tissue damage after local injection of interferon-beta is most likely immune-mediated.…”