Early systemic sclerosis—opportunities for treatment

Abstract

Systemic sclerosis (SSc) is characterized by microvasculopathy (Raynaud's phenomenon and fibrointimal proliferation), presence of autoantibodies and collagen deposition in skin (scleroderma) and internal organs. Microvasculopathy, detected by nailfold capillaroscopy, and disease-specific autoantibodies (anti-topoisomerase I, anti-centromere, anti-RNA polymerase III antibodies) usually appear earlier, even years before scleroderma. At that stage of the disease, immune activation with T cells and B cells promote fibrosis. Diagnosis of SSc has been relied on scleroderma, and by this time, internal organs may have developed fibrosis, a lethal feature with no available treatment. The new EULAR/ACR 2013 criteria for the classification of SSc will help identify SSc patients before fibrosis of internal organs. The early diagnosis of SSc, before the development of fibrosis in internal organs, will allow the introduction of immunosuppressive medications in these patients in a controlled setting (randomized trials). It is anticipated that this approach will change the hitherto grim prognosis of SSc for the better.

Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

“…Although several leaps forward have been made in understanding SSc, key events in pathogenesis and subsequent forthcoming curative therapy still needs to be developed. Fibroblasts have long been regarded as the key players in SSc pathogenesis, but as research in SSc has intensified, there is more focus now on investigating the involvement of immune system in early phase of the disease 1 2. This is supported by findings in a genome-wide association study that most genes associated with SSc susceptibility have pivotal functions within the immune system, such as CD247 , STAT4 and IRF5 3…”

Immunotherapy of systemic sclerosis

“…However, it is time to consider and prescribe mild immunosuppression in RP patients with typical nailfold capillaroscopy changes and autoAbs in a well-monitored environment. 23 Targeted therapies B1. Biological therapies as monomeric or multimeric forms) and derives from the plasma of thousands healthy individuals (3,000-80,000).…”

“…New classification criteria for SSc have been recently developed, that could help diagnose SSc early, and facilitate early recognition of SSc and offer opportunities for early therapeutic intervention. 22,23 Immunotherapy includes general immunosuppression and therapies targeting specific molecules involved in T cell and B cell survival and function (targeted therapies). Data on targeted therapies, such as biologics in the treatment of patients with SSc are emerging.…”

Multiple Perforations of the Small Intestine during Systemic Sclerosis

“…It is characterized by a fibroblastic proliferation with accumulation of dense collagen in the connective tissue, a diffuse microangiopathy, and an immunological disorder [1,2]: presence of anti-nuclear auto-antibodies, of which the most specific of SS are anti-topoisomerase I, anti-centromere, and anti-RNA polymerase III antibodies according to the clinical form of SS [4,5].…”