8Evidence-based management of rapidly progressing systemic sclerosis
Section snippets
Assessment of skin disease
Skin fibrosis is a hallmark feature of SSc. Depending on the extent of skin sclerosis, the disease is classified into two major subsets – limited cutaneous SSc (limited SSc) when only skin distal to the elbows and knees (with or without face involvement) is affected and diffuse cutaneous SSc (diffuse SSc) when the skin thickening includes distal areas and also spreads proximally. These patients are also at risk from other complications of SSc.
The majority of cases of rapidly progressive SSc can
Renal involvement in rapidly progressive SSc
The pattern of kidney manifestations in SSc may be divided into scleroderma renal crisis (SRC), chronic kidney disease and inflammatory renal pathology. However, SRC is the most important renal complication in SSc and occurs in 10–15% of patients with diffuse SSc and very rarely (1–2%) in limited SSc [11]. The mortality among patients with SRC remains high despite the early treatment with angiotensin-converting enzyme (ACE) inhibitors [12], and clear evidence that ACEi therapy has a
Interstitial pulmonary fibrosis
The commonest forms of interstitial lung disease in SSc are histologically classified as usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Investigation and assessment of interstitial lung disease in SSc focusses on early detection, severity assessment and determination of progression that is best performed by regular pulmonary function tests (PFTs). High-resolution computed tomography (HRCT) imaging remains the most valuable tool for detection of early lung
Pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH), defined as an elevation in the mean pulmonary artery pressure >25 mmHg at rest with normal pulmonary capillary wedge pressure (PCWP) on right heart catheterisation, occurs in both limited and diffuse cutaneous forms of SSc, and has major mortality. The outcome in SSc-associated pulmonary hypertension is considerably worse than that of idiopathic pulmonary hypertension [22]. This may reflect co-morbidity or differences in underlying pathogenetic mechanisms.
Cardiac involvement
Cardiac involvement is a major factor determining mortality in SSc. As with other complications, it is associated particularly with rapidly progressive diffuse SSc but current limitations in detection and diagnosis mean that the precise frequency of significant cardiac involvement in SSc has been difficult to ascertain [27]. Moreover, one potential consequence of cardiac involvement is reduction in the ability to cope well with the intercurrent haemodynamic of cardiac stress such as that due to
Gastrointestinal manifestations
The gastrointestinal tract (GIT) is the most commonly involved internal organ system (approximately 90%) in SSc, and gastro-oesophageal manifestations are the most frequent [31]. Despite major morbidity, only a minority of cases have life-threatening complications. Severe involvement of the small intestine typically occurs in patients with established SSc. At its most severe, small intestinal involvement leads to recurrent episodes of intestinal pseudo-obstruction due to ileus with dilated
Autoantibodies in assessment of SSc
The role of autoantibodies in SSc is still unclear, although there is a growing body of evidence that antibodies are potential markers of organ-based complications that impact on disease outcome. Easier assays and more systematic evaluation offers real potential in risk stratification of SSc cases since most patients can be defined by their serological profile at initial presentation [35]. The three most frequent SSc-associated antibodies – anti-centromere antibodies (ACAs), anti-topoisomerase
High-dose immunosuppressive therapy (HDIT) and autologous haematopoietic stem cell transplantation (HSCT)
Patients with severe SSc have been evaluated using HSCT. The underlying hypothesis is that upfront intensive immunosuppression would ablate immune responses driving disease activity, and the infused haematopoietic progenitors, depleted in vitro of disease-causing mature lymphoid elements (using CD34-selection), may then be able to generate a new non-autoreactive immune system [36]. Inclusion criteria included: ≤65 years, early (≤4 years), diffuse SSc and significant visceral organ involvement,
Concluding comments
As can be seen in this review, there have been substantial recent advances in the field of SSc in terms of disease assessment and therapy. This has included a greater appreciation of the strengths and limitations of current assessment techniques and a growing appreciation of the clinical diversity of SSc and heterogeneity in terms of disease progression. Thus, it is clear that in those cases that are at highest risk of life-threatening complications or progression, an aggressive approach to
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Outcomes of limited cutaneous systemic sclerosis patients: Results on more than 12,000 patients from the EUSTAR database
2020, Autoimmunity ReviewsCitation Excerpt :It is also the fundamental feature which stratifies SSc patients according to the extent of skin involvement in diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subsets [4]. In DcSSc, several studies have consistently demonstrated a robust correlation between the extent and the progression of skin fibrosis with disease prognosis [5–7]. In this subset, the measurement of skin thickness mainly through the modified Rodnan skin score (mRSS) [8] is used as surrogate measure of disease prognosis.
KIT as a therapeutic target for non-oncological diseases
2019, Pharmacology and TherapeuticsCitation Excerpt :Systemic sclerosis (SS), also called scleroderma, is an autoimmune-mediated rheumatic disease characterized by widespread vasculopathy, inflammation and multi-organ fibrosis and dysfunction (Denton and Khanna, 2017). Although several medications are used to treat the skin disease associated with systemic sclerosis, global effective therapies do not exist (Khanna and Denton, 2010). TGFβ and PDGF are cytokines implicated in the pathological fibrosis of SS (Leask and Abraham, 2004; Trojanowska, 2008).
Scleroderma–Systemic Sclerosis
2019, Clinical Immunology: Principles and PracticeAutologous hematopoietic stem cell transplantation in systemic sclerosis: A reset to tolerance?
2018, Immunology LettersCitation Excerpt :This so-called ‘poor prognosis SSc’ has a lower survival rate of 85.5% in the first 5 years, which is mostly caused by cardiopulmonary failure [3]. Therapeutic options are scarce in poor prognosis SSc [4]. Only intravenous (IV) cyclophosphamide (CYC) and methotrexate have been shown to impact disease activity, although promising clinical trials examining other therapeutic options are ongoing [5].
Adipose tissue-derived stem cells ameliorates dermal fibrosis in a mouse model of scleroderma
2017, Asian Pacific Journal of Tropical MedicineCitation Excerpt :The H-Scores for TGF-β1 and VEGF were shown as Table 3. Scleroderma is an autoimmune disease characterized by vascular injury, excessive accumulation of ECM in skin and various internal organs, and immunological abnormalities [15]. Scleroderma is classified into the following two main subsets: LS and DS.
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