Performance of the EULAR Systemic sclerosis Impact of Disease (ScleroID) questionnaire as a patient-reported outcome measure for patients with diffuse systemic sclerosis.

Objective: Systemic sclerosis Impact of Disease (ScleroID) is the first comprehensive patient-reported outcome measure (PROM) specifically developed for systemic sclerosis (SSc). We investigated the performance of ScleroID in patients with diffuse cutaneous SSc (dcSSc), as a prerequisite for its use in randomised controlled trials (RCTs) testing potentially disease-modifying drugs.

Methods: All patients with dcSSc from the large, multicentric, ScleroID cohort were included.

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets.

Background: Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as 'basket' endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials.

Nearest Consensus Clustering Classification to Identify Subclasses and Predict Disease.

Disease subtyping, which helps to develop personalized treatments, remains a challenge in data analysis because of the many different ways to group patients based upon their data. However, if we can identify subclasses of disease, then it will help to develop better models that are more specific to individuals and should therefore improve prediction and understanding of the underlying characteristics of the disease in question. This paper proposes a new algorithm that integrates consensus clustering methods with classification in order to overcome issues with sample bias.

RISE-SSc: Riociguat in diffuse cutaneous systemic sclerosis.

Unlabelled: RISE-SSc is a randomized, double-blind, placebo-controlled phase 2 study investigating the efficacy and safety of riociguat in patients with diffuse cutaneous systemic sclerosis (dcSSc). Based on positive results from riociguat trials in patients with pulmonary hypertension and chronic thromboembolic pulmonary hypertension in combination with the known antiproliferative and antifibrotic effects seen in animal models, patients with SSc may benefit from treatment with riociguat. Patients with SSc meeting the ACR/EULAR systemic sclerosis classification criteria with diffuse cutaneous SSc (dcSSc) subset per LeRoy criteria, and a disease duration of less than or equal to 18 months will be randomized to placebo or riociguat 0.

[Updated clinical classification of pulmonary hypertension].

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed.

Interstitial lung disease in systemic sclerosis.

Despite many unanswered questions regarding the pathogenesis of interstitial lung disease in systemic sclerosis (SSc-ILD) and the lack of accurate epidemiological risk factors, there have been major advances in the identification and prognostic evaluation of SSc-ILD. The evaluation of disease severity is a multidisciplinary exercise, requiring the integration of pulmonary function tests, high-resolution computed tomography data, and symptomatic severity and these factors all need to be considered in the detection of disease progression. Except in a minority of patients with reversible inflammatory disease, the primary goal of treatment is the prevention of disease progression.

Updated clinical classification of pulmonary hypertension.

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed.

Juvenile and young adult-onset systemic sclerosis share the same organ involvement in adulthood: data from the EUSTAR database.

Objective: The aim of the present study was to explore the long-term outcome and clinical characteristics of adult patients with juvenile onset in the EULAR Scleroderma Trials and Research (EUSTAR) cohort and compare them with adult patients with onset between 20 and 40 years of age.

Methods: From the EUSTAR SSc cohort two patient groups were analysed: patients with juvenile SSc (jSSc) who are adults at present, and patients diagnosed between the age of 20 and 40 years (aSSc). Demographic data of the patients, organ involvement and outcome of the disease were examined using the Minimal Essential Data Set database system.

Fecal incontinence in systemic sclerosis is secondary to neuropathy.

Objectives: Systemic sclerosis (SSc) is a chronic multi-system autoimmune disorder with gastrointestinal tract (GIT) involvement in up to 90% of patients and anorectal involvement occurs in up to 50% of patients. The pathogenesis of gastrointestinal abnormalities may be both myogenic and neurogenic. We aimed to identify which anorectal physiological abnormalities correlate with clinical symptoms and thus understand the pathophysiology of anorectal involvement in SSc.

Registries in systemic sclerosis: a worldwide experience.

SSc is a multisystem disease characterized by an unpredictable course, high mortality and resistance to therapy. The complexity and severity of SSc is a growing burden on the health-care systems. As a result, researchers are seeking new therapeutic strategies for effectively managing these patients.

Systemic Sclerosis-Associated Interstitial Lung Disease: Lessons from Clinical Trials, Outcome Measures, and Future Study Design.

Pulmonary involvement including interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (scleroderma; SSc). This article reviews the current evidence based medicine regarding available therapies for SSc-ILD ; discusses the lessons learned from recent SSc-ILD randomized controlled trials (RCTs); and proposes outcome measures and recommendations for design of future RCTs for SSc-ILD.

Signaling pathways regulating intercellular adhesion molecule 1 expression by endothelin 1: comparison with interleukin-1beta in normal and scleroderma dermal fibroblasts.

Objective: Endothelin 1 (ET-1) has been implicated in the pathogenesis of fibrotic and inflammatory diseases, including scleroderma. In addition to modulating vascular tone and extracellular matrix turnover, ET-1 up-regulates cell surface adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), which is key to cell-cell and cell-matrix adhesion and leukocyte infiltration. This study was undertaken to delineate the signal transduction pathways utilized by ET-1 and compare them with those adopted by proinflammatory cytokine interleukin-1beta (IL-1beta) in normal and scleroderma dermal fibroblasts.

The TNF-863A allele strongly associates with anticentromere antibody positivity in scleroderma.

Objective: Scleroderma is characterized by the presence of 3 predominant, yet almost mutually exclusive, antibodies: anticentromere antibody (ACA), antitopoisomerase antibody, and anti-RNA polymerase antibody. The purpose of this study was to investigate tumor necrosis factor (TNF) polymorphisms in scleroderma, with the specific aim of determining whether TNF polymorphisms would prove to be stronger markers for ACA than class II major histocompatibility complex (MHC).

Methods: We studied 214 UK white scleroderma patients and 354 healthy controls.