title: Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.
abstract: Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.
authors.affiliation: Division of Rheumatology, University Hospital Zurich, Gloriastr. 25, 8091, Zurich, Switzerland. oliver.distler@usz.ch.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: Division of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cozzio
mesh_terms: D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012594:Scleroderma, Localized / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use
chemical_list: D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D012702:Serotonin Antagonists; D006162:Guanylate Cyclase
keywords: Interleukin-6; Localized scleroderma; Nintedanib; Serotonin; Soluble guanylate cyclase; Systemic sclerosis