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Lancet (London, England) Jan 2023Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition,... (Review)
Review
Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition, research advancements have improved our understanding of its disease pathogenesis and clinical phenotypes and expanded our treatment armamentarium. Early and accurate diagnosis is essential, while ongoing efforts to risk stratify patients have a central role in predicting both organ involvement and disease progression. A holistic approach is required when choosing the optimal therapeutic strategy, balancing the side-effect profile with efficacy and tailoring the treatment according to the goals of care of the patient. This Seminar reviews the multiple clinical dimensions of systemic sclerosis, beginning at a precursor very early stage of disease, with a focus on timely early detection of organ involvement. This Seminar also summarises management considerations according to the pathological hallmarks of systemic sclerosis (eg, inflammation, fibrosis, and vasculopathy) and highlights unmet needs and opportunities for future research and discovery.
Topics: Humans; Scleroderma, Systemic; Fibrosis; Vascular Diseases; Disease Progression; Autoimmune Diseases
PubMed: 36442487
DOI: 10.1016/S0140-6736(22)01692-0 -
The Kaohsiung Journal of Medical... Mar 2022Systemic sclerosis (scleroderma) is an autoimmune-triggered chronic fibrosing disease that affects the skin and many other organs. Its pathophysiology is complex and... (Review)
Review
Systemic sclerosis (scleroderma) is an autoimmune-triggered chronic fibrosing disease that affects the skin and many other organs. Its pathophysiology is complex and involves an early endothelial damage, an inflammatory infiltrate and a resulting fibrotic reaction. Based on a predisposing genetic background, an altered balance of the acquired and the innate immune system leads to the release of many cytokines and chemokines as well as autoantibodies, which induce the activation of fibroblasts with the formation of myofibroblasts and the deposition of a stiff and rigid connective tissue. A curative treatment is still not available but remarkable progress has been made in the management of organ complications. In addition, several breakthroughs in the pathophysiology have led to new therapeutic concepts. Based on these, many new compounds have been developed during the last years, which target these different pathways and offer specific therapeutic approaches.
Topics: Adaptive Immunity; Environment; Fibrosis; Genetic Predisposition to Disease; Humans; Immunity, Innate; Scleroderma, Systemic
PubMed: 35234358
DOI: 10.1002/kjm2.12505 -
Current Opinion in Pharmacology Jun 2022Systemic sclerosis (SSc) is a rare, systemic autoimmune disease of unknown etiology. Among the systemic rheumatic diseases, SSc carries the highest mortality, in part... (Review)
Review
Systemic sclerosis (SSc) is a rare, systemic autoimmune disease of unknown etiology. Among the systemic rheumatic diseases, SSc carries the highest mortality, in part due to the historical lack of disease modifying therapies. Recently, landmark randomized controlled trials (RCTs) have been conducted that have illustrated the heterogeneous nature of SSc and furthered our understanding of the key inflammatory and fibrotic pathways involved in SSc pathogenesis. Although SSc affects various organ systems, RCTs have focused on investigating treatments for diffuse cutaneous sclerosis (dcSSc) and interstitial lung disease (ILD). While recent RCTs for dcSSc have failed to demonstrate a treatment benefit, the outcomes of two RCTs led to the approval of two novel therapies for SSc-ILD: nintedanib and tocilizumab. This review summarizes the salient outcome data from recent SSc trials within a practical clinical framework and points out gaps in knowledge that may help inform the design of future SSc studies.
Topics: Fibrosis; Humans; Lung Diseases, Interstitial; Scleroderma, Systemic; Skin
PubMed: 35447517
DOI: 10.1016/j.coph.2022.102211 -
Advances in Clinical and Experimental... Aug 2017Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin thickening as one of the most common symptoms. The disease has 2 main subsets, diffuse and... (Review)
Review
Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin thickening as one of the most common symptoms. The disease has 2 main subsets, diffuse and limited forms. The subset known as systemic sclerosis sine scleroderma (ssSSc) is a very rare subset characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. The classification of ssSSc into 3 groups was proposed. Type I (complete) is characterized by the lack of any cutaneous changes typical for the disease at least until systemic sclerosis-related insufficiency of any internal organ occurs. Type II (incomplete) is characterized by the absence of sclerodactyly, but other cutaneous involvements (e.g. calcifications, telangiectasies, pitting scars) can be found. Type III (delayed) is characterized by clinical internal organ involvement typical for systemic sclerosis that has appeared before skin changes (complete or incomplete). In general, the demographic and clinical characteristics of the ssSSc patients suggest that they are similar to those with diffuse or limited form of the disease. Diagnosis of ssSSc still remains difficult and this disease form should be considered in all cases of unexplained fibrotic involvement of the internal organs.
Topics: Disease Progression; Fibrosis; Humans; Prevalence; Prognosis; Scleroderma, Systemic; Severity of Illness Index; Terminology as Topic
PubMed: 29068586
DOI: 10.17219/acem/64334 -
Clinical Medicine (London, England) Nov 2020Raynaud's phenomenon (RP) is a common vasospastic condition which affects ~5% of the general population. The majority of individuals have primary RP; however, Raynaud's...
Raynaud's phenomenon (RP) is a common vasospastic condition which affects ~5% of the general population. The majority of individuals have primary RP; however, Raynaud's can also occur secondary to a broad range of underlying medical conditions and drug therapies. RP is a cardinal feature in patients with systemic sclerosis and is often the earliest symptom of the disease. Unlike primary RP, patients with secondary RP can develop persistent digital ischaemia, including ulcers and gangrene. Patients require a comprehensive clinical assessment and investigation, in particular, the detection of autoantibodies and nailfold capillaroscopic abnormalities. Non-pharmacological management is indicated in all patients. There are a wide range of available drug therapies to treat RP, including when complicated by digital ulceration, and surgical intervention is sometimes required. Future research is needed to understand the complex pathogenesis of RP and to measure the impact and severity of RP to develop optimised approaches to management.
Topics: Autoantibodies; Humans; Raynaud Disease; Scleroderma, Systemic
PubMed: 33199324
DOI: 10.7861/clinmed.2020-0754 -
Giornale Italiano Di Dermatologia E... Apr 2018Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for... (Review)
Review
Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for Systemic Sclerosis, developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for a patient to be classified as having scleroderma. Histological examination is not included in the diagnostic criteria and is not routinely performed. Skin biopsy is recommended only in the case of diagnostic doubt with other scleroderma like disorders (scleromyxedema, scleredema, nephrogenic systemic fibrosis). Alternatively, skin biopsy is also often performed for research purposes. Indeed, the first step analysis of new cytokines or pathways that may contribute to the pathogenesis of the disease requires the evaluation of their expression or activation in the skin of scleroderma patients compared to healthy controls. The histological picture of the skin in bot localized and systemic scleroder shows initially microvascular alterations and chronic inflammation while in the more advanced stages skin fibrosis prevails. Localized scleroderma (LS) or morphea includes a number of subtypes which are classified more according to their clinical presentation rather than histopathological pictures. However, some histopathologic changes may be useful in differentiating each entity from the others and from other sclerodermoid disorders.
Topics: Biopsy; Cytokines; Diagnosis, Differential; Humans; Scleroderma, Localized; Scleroderma, Systemic; Skin Diseases
PubMed: 29368844
DOI: 10.23736/S0392-0488.18.05922-9 -
Clinical Reviews in Allergy & Immunology Jun 2023Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality... (Review)
Review
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.
Topics: Humans; Hypertension, Renal; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Scleroderma, Systemic; Scleroderma, Localized
PubMed: 35648373
DOI: 10.1007/s12016-022-08945-x -
Clinical and Experimental Rheumatology Oct 2022Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel... (Review)
Review
Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published in the scientific community.In this review we report an overview of some of the most relevant contributions published in 2021.
Topics: Humans; Scleroderma, Systemic; Fibrosis; Autoimmune Diseases; Skin
PubMed: 36135958
DOI: 10.55563/clinexprheumatol/3401fl -
European Respiratory Review : An... Sep 2021Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a... (Review)
Review
Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a heterogenous condition and several different forms can be associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to left heart disease and PH due to interstitial lung disease. The incidence of pulmonary veno-occlusive disease is also increased. Accurate and early diagnosis to allow optimal treatment is, therefore, essential. Recent changes to diagnostic haemodynamic criteria at the 6th World Symposium on Pulmonary Hypertension have resulted in therapeutic uncertainty regarding patients with borderline pulmonary haemodynamics. Furthermore, the optimal pulmonary vascular resistance threshold for diagnosing PAH and the role of exercise in identifying early disease require further elucidation. In this article we review the epidemiology, diagnosis, outcomes and treatment of the spectrum of pulmonary vascular phenotypes associated with SSc.
Topics: Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Phenotype; Pulmonary Arterial Hypertension; Scleroderma, Systemic
PubMed: 34407977
DOI: 10.1183/16000617.0053-2021 -
Clinical and Experimental Rheumatology Aug 2023Systemic sclerosis is a rare and chronic connective tissue disease resulting from an intricate pathogenesis and is expressed in very heterogeneous clinical... (Review)
Review
Systemic sclerosis is a rare and chronic connective tissue disease resulting from an intricate pathogenesis and is expressed in very heterogeneous clinical manifestations. Every year many studies try to unravel and shed new insight into the pathogenesis, organ involvement and treatment of this complex and severe disease. We herein provide an overview of the most relevant studies published in the literature in 2022.
Topics: Humans; Scleroderma, Systemic; Connective Tissue Diseases
PubMed: 37199215
DOI: 10.55563/clinexprheumatol/ki76s5