Cutaneous Adverse Events Associated with Interferon-β Treatment of Multiple Sclerosis

Abstract

Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

Epidermal growth factor receptor inhibitors trigger a type I interferon response in human skin

“…Impairment of the EGFR/Ras/Raf/MEK/ERK cascade by anti-EGFR, anti-Raf, or anti-MEK anti-cancer drugs could enhance type I IFN response, giving rise to inflammatory events in the skin and possibly also in the intestinal tract, the two most important targets of their adverse events [13]. Indeed, type I IFNs frequently do cause dermatological side effects [45]. Subcutaneous injections of IFN-β in multiple sclerosis patients were shown to initiate an inflammatory skin reaction characterized by enhanced CCL2, CCL5 and CXCL10 in keratinocytes and infiltrating leucocytes [15], actually the same chemokines strongly up-regulated in response to EGFR inhibition in human and mouse keratinocytes, in vitro and in vivo [8–11, 14].…”

Therapeutic Elimination of the Type 1 Interferon Receptor for Treating Psoriatic Skin Inflammation

“…Although correlative evidence from human studies (Afshar et al, 2013, Tas and Atsu, 2015, Kolb-Maurer et al, 2015, Baechler et al, 2006) and results obtained in human psoriatic skin grafted onto immunocompromised mice (Nestle et al, 2005) suggested the role of IFN in psoriatic inflammation, the mechanistic importance of IFN signaling remained controversial based on variable strength of attenuation of the imiquimod-induced inflammation in Ifnar1 -null mice (Grine et al, 2015, Wohn et al, 2013). The latter phenotype might have been underestimated because it was compared with wild type mice where wild type IFNAR1 can undergo accelerated inflammation-induced ubiquitination and downregulation.…”

“…Several lines of evidence suggest the importance of IFN in the pathogenesis of psoriasis. First, iatrogenic development or exacerbation of psoriasis associated with the use of pharmacologic IFN was reported in patients who received IFN to treat hepatitis C, multiple sclerosis, or malignant melanoma (Afshar et al, 2013, Tas and Atsu, 2015, Kolb-Maurer et al, 2015). Second, induction of the IFN-stimulated gene expression signature has been described in samples from psoriasis patients (Baechler et al, 2006, Kim and Krueger, 2015).…”

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

“…Another trait particularly shared amongst different antibody-driven AID is the expression of a T1-IFN signature in both blood- and disease-affected tissue (232–234), the strength of which generally correlates with disease activity and severity (235–238). Vice versa , T1-IFN immunotherapy as treatment for other diseases is known to cause symptoms similar to those observed in AID, such as development of psoriatic lesions in MS or hepatitis C-infected patients (239, 240). …”