Systemic Sclerosis - An Update

Abstract

Systemic sclerosis (SSc) is a clinically heterogeneous, systemic disorder affecting connective tissue of skin, internal organs, and walls of blood vessels. It is characterized by alterations of the microvasculature in the form of hypoxia, digital ulcers, and pulmonary arterial hypertension; disturbances of the immune system, including dysbalance of cytokine expression, autoantibodies (Auto-ab), and abnormalities of blood progenitor and/or effector cells; and by massive deposition of collagen in the connective tissue of the skin and various internal organs. This review discusses epidemiology and survival; clinical features including subsets and internal organ involvement; pathophysiology including genetics, microvasculature, immunobiology, fibroblasts (FBs), and connective tissue metabolism; and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder. Therapy involves immunomodulation and targeting of blood vessels and fibrosis. The multicenter online database “European Scleroderma Trials and Research” project allows further insight of prognostic factors and conception of new therapies. Physical and psychotherapy are important. * SSc : systemic sclerosis ARA : American Rheumatism Association ANA : antinuclear antibodies ACA : anti-centromere antibody CREST : calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, teleangiectasia ATA : anti-topoisomerase antibodies ACE : angiotensin-converting enzyme MHC : major histocompatibility complex SNPs : single nucleotide polymorphisms IRF5 : interferon regulatory factor 5 Stat4 : signal transducer and activator of transcription 4 PTPN22 : protein tyrosine phosphatase, non-receptor type 22 BANK1 : B cell scaffold protein with ankyrin repeats 1 CTGF : connective tissue growth factor TBX21 : T-box transcription factor IL-10R : interleukin 10 receptor IL-23R : interleukin 23 receptor TNFSF4 : tumor necrosis factor superfamily PCR : polymerase chain reaction GvH : graft vs host TGFβ : transforming growth factor beta PDGF : platelet-derived growth factor EC : endothelial cells NO : nitric oxide EDRF : endothelial dependent relaxation factor HIF : hypoxia-induced factor VEGF : vascular endothelial growth factor AECA : anti-endothelial cell antibodies CMV : cytomegalovirus vWF : von Willebrand factor IL : interleukin LFA-1 : lymphocyte function-associated antigen 1 BAFF : B cell activating factor dSSc : diffuse cutaneous SSc SI-SSc : silica-associated SSc RNAP : RNA polymerase MMP : matrix metalloproteinase ECM : extracellular matrix PDGFR : platelet derived growth factor receptor ROS : reactive oxygen species INF : interferon TNF-α : tumor necrosis factor-alpha PN-1 : protease nexin-1 AT : angiotensin PGI2 : prostacyclin PHT : pulmonary hypertension UVA : ultraviolet A PUVA : photochemotherapy with UVA HSCT : hematopoietic stem cell transplantation Auto-ab : autoantibodies ADCC : antibody-dependent cell cytotoxicity TF : tissue factor VCAM : vascular cell adhesion molecule ICAM : intercellular adhesion molecule E-sel : E-selectin PMNC : polymorphonuclear cells FB : fibroblast rec : receptor ERK 1/2 : extracellular-signal-regulated kinases 1 and 2 MCP-1 : monocyte chemoattractant protein TACE : TNF-α converting enzyme IFN-α : interferon-α