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

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..

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

roadmap to vasculitis a rheumatological treasure hunt part ii classification features of individual vasculitides and differential diagnosis against pseudovasculitis

Abstract Since the triggering factors causing primary vasculitides are by definition not (yet) known, we have to classify them to clinical syndromes based on the size, site, type and effect of the blood vessel involvement. ACR classification criteria and Chapel Hill nomenclature are useful tools to familiarize with the primary vasculitides, although a lot of criticism has been voiced in the literature indicating that they only represent the best available consensus. The present text takes advantage of the recent developments such as introduction of the anti-neutrophilic cytoplasmic auto (ANCA) antibodies, and divides the vasculitides to those affecting typically the large, medium and small arteries or only small blood vessels. In addition, some vasculitides, which are still difficult to place to the vasculitis map, like Burger's disease, Goodpasture's syndrome, primary angiitin of the central nervous system (PACNS) and panniculitis, are dealt with. As it is a long and winding road, attention has to be paid to the clinical details to follow the road sign to "pseudovasculitis", when that is the right way to go. They represent a bunch of non-vasculitic conditions, which lead to structural or vasospastic impairment of the blood flow, bleeding or thromboembolism and hyperviscosity. These imitators have to some extent, similar clinical symptoms and signs as well as laboratory and radiological findings to those found in true systemic vasculitides. This also emphasizes the importance of internal medicine as the intellectual (albeit not necessarily organizational) home of rheumatology and rheumatologists as we deal with conditions like atherosclerosis, antiphospholipid antibody syndrome, infectious endocarditic, myxoma of the heart and cholesterol embolism

roadmap to vasculitis a rheumatological treasure hunt

Abstract Vasculitis is characterized by inflammation of the wall of blood vessels. It involves immunologically mediated responses to usually unknown antigens, which result in vessel wall damage. Weakening of the vessel wall can lead to aneurysms, dissections or bleeding and narrowing of the lumen (caused by vasculitis per se and complicating thrombosis and embolization) resulting in ischemic damage and necrosis of the affected end organs and tissues. The first part of this four-part review describes the red flags and stop signs, which could help the busy doctor to stop and to start to think of the possibility of vasculitis. This is particularly important as many of these syndromes are life-threatening and hence their diagnostics can be compared to "a rheumatologic treasure hunt" as the treasured life of the patient is often at stake. Everything starts with simple measures, namely taking the patient history and conducting a complete physical examination. This is often enough for the identification of triggering factors as causes as well as targets of therapy in secondary vasculitides. They are often also enough for the right diagnosis, which only needs to be confirmed, perhaps by specialists, with more elaborate and expensive methodology