UNASSIGNED: Scleroderma is a multisystemic disorder characterised by inflammatory and vascular anomalies, and excess fibrosis. Progressive systemic sclerosis (PSS) mainly progresses with skin, joint, lung, heart, and kidney involvement. Involvement of cerebral vessels is rare in both localised scleroderma and PSS. Transient ischemic attack and stroke are rare complications of scleroderma.
UNASSIGNED: We present a 60-year-old stroke patient with localised scleroderma presenting with impaired speech, forgetting words, and occasional temporary memory loss.
UNASSIGNED: In the case we present, no pathology was found in the clinical and laboratory tests performed in terms of ischemic risk factors. Skin findings included contracture, skin biopsy results, and antibody positivity related to scleroderma. Given the current pathogenesis of scleroderma, the patient was suspected of having a stroke.

This study aimed to clarify the association of HLA Class I and II with dcSSc and lcSSc in Thais. HLA typing for 11 gene loci (Class I: HLA-A, B and C, and Class II [HLA-DR, DP and DQ]) was carried out using the Next Generation DNA Sequencing method (three fields) in 92 Thai patients with systemic sclerosis (55 dcSSc, 37 lcSSc) and 135 healthy controls (HCs). The distribution of HLA alleles in patients with dcSSc and lcSSc was compared. When compared with HCs, the AF of A*24:02:01, A*24:07:01, B*27:04:01 and B*27:06 showed an increasing trend in lcSSc patients without statistical significance. DRB1*15:02:01, DRB5*01:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01 increased significantly in dcSSc patients. DQB1*05:01:24 and DPB1*13:01:01 also increased significantly in lcSSc patients, but less significantly than in dcSSc patients. The association of DPB1*05:01:01 with lcSSc was significantly protective. HLA-A*24:02:01, B*27:06 and C*03:04:01 formed a three-locus haplotype that also constituted an eight-locus haplotype with DRB1*15:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01. There was a possibility that HLA Class I would play a role in the pathogenesis of lcSSc, while Class II played more of a role in the dcSSc in Thai patients.

In systemic sclerosis (SSc, or scleroderma), defective angiogenesis, clinically manifesting with abnormal capillary architecture and severe capillary reduction, represents a hallmark of early-stage disease, usually preceding the onset of tissue fibrosis, and is caused by several cellular and molecular mechanisms affecting microvascular endothelial cells with different outcomes. Indeed, once damaged, endothelial cells can be dysfunctionally activated, thus becoming unable to undergo angiogenesis and promoting perivascular inflammation. They can also undergo apoptosis, transdifferentiate into profibrotic myofibroblasts, or acquire a senescence-associated secretory phenotype characterized by the release of exosomes and several profibrotic and proinflammatory mediators. In this narrative review, we aimed to give a comprehensive overview of recent studies dealing with the cellular and molecular mechanisms underlying SSc defective angiogenesis and the related endothelial cell dysfunctions, mainly the endothelial-to-mesenchymal transition process. We also discussed potential novel vascular treatment strategies able to restore the angiogenic process and reduce the endothelial-to-mesenchymal transition in this complex disease.

UNASSIGNED: To study the prevalence of Helicobacter pylori in systemic sclerosis patients and its gastrointestinal manifestations in comparison with Helicobacter pylori-negative systemic sclerosis patients. Systemic sclerosis gastrointestinal outcome post Helicobacter pylori eradication was evaluated.
UNASSIGNED: In total, 70 systemic sclerosis patients and 70 age-, gender- and race-matched healthy controls had their urea breath test done. Gastrointestinal manifestations in systemic sclerosis were assessed using University of California at Los Angeles 2.0 and Leeds Dyspepsia Questionnaire questionnaires. Systemic sclerosis patients with confirmed Helicobacter pylori infection were given standard Helicobacter pylori eradication therapy. Urea breath test was repeated 6 weeks posteradication therapy with their gastrointestinal symptoms reassessed.
UNASSIGNED: The prevalence of Helicobacter pylori was low in both systemic sclerosis patients (10%) and healthy controls (2.9%). There was no significant difference in gastrointestinal symptoms between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. However, the Helicobacter pylori-positive patients reported higher median severity scores for the gastrointestinal symptoms of reflux (0.5 vs 0.35), abdominal distension (1.5 vs 0.75) and social functioning impairment score (0.5 vs 0.16) using the University of California at Los Angeles 2.0 score. The Helicobacter pylori-positive patients also indicated increased upper abdominal pain (3.0 vs 0.0), regurgitation (2.0 vs 0.0) and burping (3.0 vs 0.0), observed from the Leeds Dyspepsia Questionnaire scores. Gastrointestinal outcomes post-Helicobacter pylori eradication showed either an improvement or complete resolution of symptoms.
UNASSIGNED: Gastrointestinal symptoms in systemic sclerosis patients are unlikely to be caused by Helicobacter pylori in the recent years in our cohort of patients. No significant difference in gastrointestinal symptoms was seen between Helicobacter pylori-positive and Helicobacter pylori-negative systemic sclerosis patients. Helicobacter pylori can be readily tested by urea breath test to look for present infection.

Oral and dental manifestations of scleroderma are extremely common, yet they are often overlooked within rheumatology and poorly understood within dentistry. Previous research has indicated the need to understand the oral and dental experiences of people living with scleroderma and those involved in their care. This scoping review aims, for the first time, to comprehensively map what is known regarding the identification and management of oral and dental manifestations of scleroderma, how these are experienced by people living with scleroderma, and to explore key characteristics of barriers and enablers to good oral and dental care in scleroderma. A scoping review was conducted using six databases (Embase, PubMed, PsychINFO, ASSIA, Scopus and SSCI), according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses - extension for Scoping Review. Grey literature was also included. Studies were eligible for inclusion if the full text and abstract were available in English, published between 2002 and 2022, and focused on the concept of oral and dental care in adults with scleroderma, either relating to identification and management, enablers and barriers to best practice, or patient experiences and well-being. Qualitative research which seeks to understand patients\' lived experiences was a notable gap in the literature. Similarly, there was a significant lack of focus on the oral and dental manifestations of scleroderma in rheumatology. Three key features were identified which would facilitate best practice in research and clinical contexts: the necessity of multidisciplinary care; the necessity of centralising patient experience; and the necessity of mitigating barriers to dental care. We conclude that increased awareness of scleroderma within dentistry and streamlining referral procedures between the disciplines of dentistry and rheumatology, to enable the early identification and management of scleroderma, are crucial.

UNASSIGNED: People with systemic sclerosis (SSc) face barriers to physical activity. Few studies have described physical activity in SSc, and none have explored physical activity longitudinally during COVID-19. We evaluated physical activity from April 2020 to March 2022 among people with SSc.
UNASSIGNED: The Scleroderma Patient-centred Intervention Network (SPIN) COVID-19 Cohort was launched in April 2020 and included participants from the ongoing SPIN Cohort plus external enrolees. Participants completed measures bi-weekly through July 2020, then every 4 weeks afterwards (28 assessments). Physical activity was assessed via the self-reported International Physical Activity Questionnaire-Elderly. Analyses included estimated means with 95% confidence intervals for physical activity across assessments. Missing data were imputed for main analyses. Sensitivity analyses included evaluating only participants who completed >90% of items for >21 of 28 possible assessments (\'completers\') and stratified analyses by sex, age, country and SSc subtype.
UNASSIGNED: A total of 800 people with SSc enrolled. Mean age was 55.6 (standard deviation (SD) = 12.6) years. Physical activity significantly decreased from April 2020 to March 2021 (standardized mean difference (SMD) = -0.17, 95% confidence interval (CI) = -0.26 to -0.07) and was stable from March 2021 to March 2022 (SMD = -0.05, 95% CI = -0.15 to 0.05). Results were similar for completers and subgroups. The proportion of participants who met World Health Organization minimum physical activity recommendations of at least 150 min of moderate-to-vigorous activity per week ranged from 63% to 82% across assessments.
UNASSIGNED: Physical activity decreased by a relatively small amount, on average, across the pandemic. Most participants met recommended physical activity levels.

UNASSIGNED: The objectives were to explore rheumatologists\' current clinical screening practices of pulmonary arterial hypertension in patients with systemic sclerosis in the United Kingdom and to identify barriers to screening and consider potential solutions.
UNASSIGNED: A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment and patient education. The survey was disseminated among rheumatologists working in the United Kingdom.
UNASSIGNED: Forty-four rheumatologists working in the United Kingdom participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised systemic sclerosis units (university or general hospitals (54.5% and 45.4%, respectively)). The majority recognised that systemic sclerosis-pulmonary arterial hypertension is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for systemic sclerosis-pulmonary arterial hypertension, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to systemic sclerosis-pulmonary arterial hypertension screening, with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions.
UNASSIGNED: Screening patients with systemic sclerosis for pulmonary arterial hypertension is crucial to improve survival, but variable practices exist among UK rheumatologists. Solutions include educating healthcare professionals on guidelines, sharing information between centres and integrating care services.

Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.

Systemic sclerosis (SSc) represents a rare and intricate autoimmune connective tissue disease, the pathophysiology of which has not been fully understood. Its key features include progressive fibrosis of the skin and internal organs, vasculopathy and aberrant immune activation. While various anti-nuclear antibodies can serve as biomarkers for the classification and prognosis of SSc, their direct role in organ dysfunction remains unclear. Anti-Th/To antibodies are present in approximately 5% of SSc patients, and are particularly prevalent among those with the limited subtype of the disease. Although the presence of these autoantibodies is associated with a mild course of the disease, there is a strong connection between them and severe clinical manifestations of SSc, including interstitial lung disease, pulmonary arterial hypertension and gastrointestinal involvement. Also, the additional clinical correlations, particularly with malignancies, need further research. Moreover, the disease\'s course seems to be influenced by antibodies, specific serum cytokines and TLR signaling pathways. Understanding the relationships between presence of anti-Th/To, its molecular aspects and response to treatment options is crucial for the development of novel, personalized therapeutic techniques and should undergo profound analysis in future studies.

Systemic sclerosis is a systemic connective tissue disease whose main pathophysiological mechanism is a progressive fibrosis of internal organs and skin leading to thickening and induration. Blood vessels may also be involved. However, systemic scleroderma is not the only disease causing cutaneous sclerosis. There is a group of diseases that mimic scleroderma in their clinical presentation - these are scleroderma-like syndromes. A distinction can be made between syndromes of inflammatory/autoimmune, genetic, metabolic, toxic, drug-induced, occupational, paraneoplastic and syndromes caused by deposition disorders. In the following paper, we have reviewed the literature on scleroderma-like syndromes. We have outlined the factors predisposing to the development of each disease, its pathogenesis, clinical presentation, diagnostic and treatment process and the differences between each syndrome and systemic scleroderma.