Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

Abstract

Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. Areas Covered This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification. Expert Opinion The extent, severity, and rate of progression of SSc skin and internal organ involvement determines the optimal therapeutic interventions for SSc. Cyclophosphamide for progressive SSc-associated interstitial lung disease and mycophenolate for rapidly progressive cutaneous involvement have shown effectiveness. Methotrexate has been used for less severe skin progression and for patients unable to tolerate mycophenolate. Rituximab was shown to induce improvement in SSc-cutaneous and lung involvement. Autologous bone marrow transplantation is reserved for selected cases in whom poor survival risk outweighs the high mortality rate of the procedure. Novel agents capable of modulating fibrotic and inflammatory pathways involved in SSc pathogenesis, including tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors are currently under development for the treatment of rapidly progressive SSc.

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

“…To reduce the EndoMT in systemic sclerosis-associated interstitial lung disease, cyclophosphamide is administered by clinicians, whereas mycophenolate or methotrexate has been used for less severe skin progression. Novel agents capable of modulating fibrotic and inflammatory pathways involved in systemic sclerosis pathogenesis include tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors [168]. As for natural compounds, geniposide (an iridoid glycoside isolated from the gardenia plant) and glycyrrhizin (a saponin of Glycyrrhiza glabra or liquorice root) seem to be promising.…”

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis

“…Following this approach of a reduced HRCT with focused apico-basal gradient we believe, that in particularly subtle changes for example in ground glass pattern may be earlier quantitatively detected especially in early stage SSc patients during follow up examinations, which even an experienced radiologic eye possibly could miss. Particularly in SSc patients with rapid disease progression one important key parameter is to detect increasing ILD at the earliest time point as possible, and not the general detection of ILD alone, because in this situation immediately progressive treatment initiation is recommended by the experts (10,46). In this context Mendoza et al even recommend the performance of standard HRCT every 6-8 months for the first 2 years after time point of diagnosis (46), assuming a higher benefit for the patient in case of early detection of disease progression compared to radiation dose protection.…”

Scleroderma-related interstitial lung disease

“…showed a small but significant improvement in FVC and quality of life [11]. However this improvement did not persist 12 months after the cessation of cyclophosphamide strongly suggesting the need for continued maintenance therapy [12]. The second trial by Hoyles et al.…”

“…In 2015, a study looking at the safety and effectiveness of Mycophenolate Mofetil reported that this drug might be beneficial in the stabilization of lung function in SSc-ILD, although the significance and longevity of this benefit remains uncertain [13]. Other single center studies and case reports have documented stabilization of pulmonary function tests and imaging scores with the use of Mycophenolate Mofetil in patients who did not respond to cyclophosphamide [14], although this difference was only noted in patients with a shorter disease course [12]. Tashkin et al.…”