Rheumatologic rehabilitation: the great expectation for rheumatic patients

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Future targets in the management of systemic sclerosis

CTDs—such as SSc and SLE and related rheumatic diseases such as RA—have complex, underlying pathogeneses that include fibrosis, vascular dysfunction, activation of the immune system and inflammation. Although some current therapies for SSc offer benefits to patients, there is a clear need to investigate potential therapeutic targets. However, the breadth and diversity of cellular pathways and mediators implicated in these diseases, coupled with inherent redundancies in these systems, has made pre-clinical investigation difficult. Despite this, recent advances have been made in elucidating the immunological aspects of CTD, including the roles of B cells, T cells, matrix-remodelling cells and autoantibodies, enabling novel therapeutic approaches including immunoablation to be investigated. The mechanisms underlying the fibrosis that characterizes SSc are also becoming clearer; and as the putative events that trigger excessive collagen deposition are identified, so too are potential junctures at which these aberrant processes may be deactivated. Progress is also being made in understanding the vasculopathy in SSc, and the potential benefits of antioxidants and endothelin receptor antagonists. There have been some significant advances in the treatments available to SSc patients; however, this spectrum of diseases remains challenging, and continues in some cases to be associated with high morbidity, increased mortality and poor prognosi

ANCA in systemic sclerosis, when vasculitis overlaps with vasculopathy: a devastating combination of pathologies

In patients with systemic sclerosis (SSc), the coexistence of ANCA-associated vasculitis (SSc-AAV) has been reported to be associated with a severe disease course, including significant pulmonary and renal involvement. The presence of ANCA is not uncommon in patients with SSc and therefore clinicians must maintain a high index of clinical suspicion about SSc-AAV. p-ANCA and anti-MPO antibodies are the most common antibodies observed. Patients typically present with clinical features of microscopic polyangiitis or renal-limited vasculitis There are multiple areas of potential interaction in the pathogenesis of SSc and AAV which can exacerbate/compound vascular disease. In addition, similar patterns of major internal organ involvement (e.g., lung and kidneys) are seen in both conditions. We highlight a diagnostic approach to SSc-AAV and the paucity of data to inform management. As such, SSc-AAV is typically treated as per isolated AAV which can potentially be hazardous in patients with SSc (e.g., the association between high-dose steroid and scleroderma renal crisis). We propose that this rare clinical entity warrants rigorous investigation including definition of a therapeutic strategy to ameliorate the potentially devastating combination of pathologies in SSc-AAV

Author Correction: Raynaud phenomenon and digital ulcers in systemic sclerosis

Correction to: Nature Reviews Rheumatology (2020) https://doi.org/10.1038/s41584-020-0386-4, published online 25 February 2020

Vasculogenesis and angiogenesis: vascular damage in systemic sclerosis

La sclerosi sistemica (SSc) è una malattia multisistemica del connettivo caratterizzata dalla presenza di alterazioni microvascolari con deficit angiogenetico (1). Suddividendo la patogenesi della SSc in momenti successivi è possibile considerare il microcircolo come la struttura colpita dalla malattia che in più fasi coinvolge l’organismo del paziente affetto da SSc (2). La cellula endoteliale (CE) viene inizialmente attivata tramite una noxa ignota alla produzione di molecole di adesione, chemiochine, citochine e fattori di crescita. In tal modo viene facilitato il passaggio (homing) linfocitario nei tessuti. Inizialmente si ha un danno a carico della CE seguito da un ispessimento dell’intima e da un progressivo restringimento del lume fino alla completa ostruzione del vaso..

Guidelines for initiation of anti-tumour necrosis factor therapy in rheumatoid arthritis: similarities and differences across Europe.

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Mechanisms of vascular damage in SSc—implications for vascular treatment strategies

Vascular abnormalities are a major component of SSc, but little is known about the events or mechanisms that initiate vascular injury and prevent its repair. In SSc, angiogenesis is incomplete or lacking despite the increased expression of a large array of pro-angiogenic factors such as VEGF. Conflicting results have recently been published concerning the presence and role of vasculogenesis and circulating endothelial progenitor cells in SSc. It remains to be established if these endothelial progenitor cells are a marker of endothelial disease or a cause of insufficient vascular repair. Human mesenchymal stem cells (MSCs) may be an alternative source for endothelial progenitor cells, and it has been observed that the angiogenic potential of endothelial-like MSCs is reduced. Other mechanisms of vascular damage include oxidative stress and factors released from activated platelets. In addition, growth factors such as ET-1 and PDGF induce proliferation of vascular smooth muscle cells resulting in intimal thickening. For the development of new therapeutic strategies, it is important to realize that the different vascular pathologies—uncompensated loss of capillaries on one hand and vascular remodelling with a proliferative vasculopathy on the other—might require different treatment approache