-
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 -
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 -
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 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 -
Medicine Nov 2022The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc... (Review)
Review
The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.
Topics: Adult; Male; Female; Humans; Scleroderma, Localized; Prospective Studies; Quality of Life; Scleroderma, Systemic; Gastrointestinal Diseases
PubMed: 36397401
DOI: 10.1097/MD.0000000000031780 -
Current Opinion in Rheumatology Nov 2022The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high... (Review)
Review
PURPOSE OF REVIEW
The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high prevalence of gastrointestinal involvement in SSc, the strategies pertaining to the assessment and treatment for this clinical dimension of SSc have historically been limited. However, the present review highlights recent research contributions that enhance our understanding of SSc-GI patient subsets and provides updates on pathogenic mechanisms of disease, assessment and symptom-directed management.
RECENT FINDINGS
In the past few years, several studies have identified risk factors for more severe gastrointestinal disease in SSc and have provided insight to optimize diagnosis and management of SSc-GI symptoms. This article also provides a review of currently available investigations and therapies for individual SSc-GI disease manifestations and reflects on actively evolving areas of research, including our understanding the role of the gut microbiome in SSc.
SUMMARY
Here, we provide important updates pertaining to the risk stratification, assessment, diagnosis and management of SSc patients with gastrointestinal symptoms. These findings provide opportunities to enhance patient care and highlight exciting opportunities for future research.
Topics: Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Risk Factors; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35993874
DOI: 10.1097/BOR.0000000000000899 -
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