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The article presents the discussion on concern raised by Andreasson and colleagues in response to the rituximab trial being tested B-cell depletion as a therapy for systemic sclerosis (SSc).

Background: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. Methods: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ − 2.5 or ≥ + 2.5 with a standard deviation not crossing zero. Results: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. Conclusions: This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: The author declares consulting agreements with AstraZeneca and Aisa Pharma.

Objective: In systemic sclerosis (SSc) patients, fatigue is the highest ranked symptom affecting quality of life (QoL), followed by Raynaud phenomenon (RP). We report results from a pilot study (NCT04854850) of the Apollo wearable device in SSc patients., Methods: Twenty-five adult participants with SSc, moderate fatigue and RP were enrolled. Participants completed a 4-week intervention, during which they wore the Apollo device daily for a minimum of 15 minutes. The primary outcome was change on the PROMIS-Fatigue 13a (PROMIS-Fatigue) scale at 4 weeks. (ClinicalTrials.gov Identifier: NCT04854850) RESULTS: After 4 weeks of using the Apollo wearable, participants reported less fatigue on the PROMIS-Fatigue (p <0.001) scale. The average daily number of RP attacks declined (p < 0.01), as did the Raynaud condition score (p<0.001) after 4 weeks of use. Average device usage (2.87 hours per day) far exceeded the requested time, and no adverse events occurred. The PROMIS-29 sub scores assessment demonstrated quality of life (QoL) improvement in physical function (p <0.01), sleep disturbance (p = 0.001), and ability to participate in social roles and activities (p < 0.001). Significant improvements were also noted for depression (p < 0.01) and disability (p < 0.05) measures., Conclusion: Use of the Apollo wearable for four weeks was associated with improvement in fatigue and RP symptom in SSc patients, with improved QoL measures and lower depression scores. Future studies should further test the efficacy of the Apollo wearable in these domains and SSc patient QoL.

Cutaneous telangiectasia (Tel) are visible permanently dilated postcapillary dermal venules and are one of the most common disease-specific manifestations of systemic sclerosis (SSc). Telangiectasia have long been recognised for their utility in the diagnosis and classification of SSc, but the clinical and prognostic relevance of these aberrant cutaneous vascular manifestations has been somewhat neglected by clinicians. Similarly, the impact of SSc-Tel on body image dissatisfaction and social discomfort has been under-appreciated. The paucity of evidence-based approaches to management has limited access to potential effective treatments for SSc-Tel. The present review examines the pathogenesis, diagnostic value, impact and clinical relevance of telangiectasia in SSc. We highlight the potentially overlooked prognostic value and clinical utility of SSc-Tel, as part of a broader appraisal of areas of unmet research need., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JDP has undertaken consultancy work, received educational support and/or speaker honoraria from Janssen, Astra Zeneca, Boehringer-Ingelheim, CSL Vifor, IsoMab, Permeatus Inc, and Sojournix Pharma. LKH has received research or consulting support from Boehringer-Ingelheim, Cumberland Pharmaceuticals, CSH Behring, Mitsubishi Tanabe Pharma Corporation, Horizon Pharmaceuticals, Biotest. AAS has received research support for clinical trials from Arena Pharmaceuticals, Kadmon Corporation, Eicos Sciences and Medpace LLC. RTD has received support in the form of consulting fees from AstraZeneca, Aisa Pharma and CSL Behring., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Systemic sclerosis (SSc) is considered a relative, or in some cases, absolute contraindication for radiation therapy for various cancers; however, radiation is the standard of care and the best option for tumor control for locally advanced head and neck (H&N) cancer. We present a case series to document postradiation outcomes in patients with SSc and H&N cancer., Methods: Patients with SSc and H&N cancer treated with radiation were identified from the Johns Hopkins Scleroderma Center and the University of Pittsburgh Scleroderma Center research registries. Through chart review, we identified whether patients developed predetermined acute and late side effects or changes in SSc activity from radiation. We further describe therapies used to prevent and treat radiation-induced fibrosis., Results: Thirteen patients with SSc who received radiation therapy for H&N cancer were included. Five-year survival was 54%. Nine patients (69%) developed local radiation-induced skin thickening, and 7 (54%) developed reduced neck range of motion. Two patients required long-term percutaneous endoscopic gastrostomy use due to radiation therapy complications. No patients required respiratory support related to radiation therapy. Regarding SSc disease activity among the patients with established SSc before radiation therapy, none experienced interstitial lung disease progression in the postradiation period. After radiation, one patient had worsening skin disease outside the radiation field; however, this patient was within the first year of SSc, when progressive skin disease is expected. Treatment strategies to prevent radiation fibrosis included pentoxifylline, amifostine, and vitamin E, while intravenous immunoglobulin (IVIG) was used to treat it., Conclusion: Although some patients with SSc who received radiation for H&N cancer developed localized skin thickening and reduced neck range of motion, systemic flares of SSc were uncommon. This observational study provides evidence to support the use of radiation therapy for H&N cancer in patients with SSc when radiation is the best treatment option., Competing Interests: Disclosures Dr Domsic received consulting fees from Astra Zeneca and Aisa pharmaceuticals. Dr Shah received grant support for clinical trials from Kadmon Corporation, Arena Pharmaceuticals, Medpace LLC, and Eicos Sciences. Dr Paik receives royalties from UpToDate. Dr Hummers received grant support for clinical trials through Horizon Pharmaceuticals, Astra Zeneca, Merck, Glaxo Smith Kline, Kadmon Corporation, Cumberland Pharmaceuticals, Boehringer Ingelheim, and Mitsubishi Tanabe., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY)., Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints)., Conclusions: The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.

Purpose of Review: Systemic sclerosis (SSc) is a chronic, multisystem, autoimmune disease characterized by fibrosis, vasculopathy and immune system dysregulation. We provide a comprehensive review of features of systemic sclerosis that can potentially present to the allergist., Recent Findings: A thorough understanding of the management options is crucial for clinicians involved in the care of patients with SSc to optimize clinical outcomes. Management of systemic sclerosis has drastically changed in the last decade and continues to evolve. This review provides an overview of management strategies for the various symptoms including skin, upper and lower airway, gastrointestinal and vascular manifestations. Institution of treatment early in the disease, including referral to rheumatology or specialized scleroderma centers, can help to both prevent and manage disease complications, and improve patient quality-of-life. While the landscape of systemic sclerosis management has evolved, we continue to recognize that there is still a need for better biomarkers and targeted therapies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore, from patients' perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients., Methods: Forty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance., Results: Twenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants' lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery., Conclusions: This large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients' lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers., Methods: Patients with PMR were identified in the American College of Rheumatology Rheumatology Informatics System for Effectiveness registry from 2016 to 2022. Use of glucocorticoids and immunomodulatory antirheumatic medications used as steroid-sparing agents were examined overall and in a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. In these new patients, multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and steroid-sparing agent use at 12 to 24 months., Results: A total of 26,102 patients with PMR were identified, of which 16,703 new patients were included in the main analysis. Patients were predominantly female (55.8%) and White (46.7%), with a mean age of 72.0 years. Hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%), and ischemic heart disease (36.0%) were the most prevalent comorbidities. At baseline, 92.3% of patients were on glucocorticoids, and only 13.1% were on a steroid-sparing agent. At 12 to 24 months, most patients remained on glucocorticoids (63.8%). Although there was an increase in use through follow-up, antirheumatic medications were prescribed only to a minority (39.0%) of patients with PMR., Conclusion: In this large US-based study of patients with PMR receiving rheumatology care, only a minority of patients were prescribed steroid-sparing agents during the first 24 months of follow-up; most patients remained on glucocorticoids past one year. Further identification of patients who would benefit from steroid-sparing agents and the timing of steroid-sparing agent initiation is needed., (© 2023 American College of Rheumatology.)

Objectives: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD)., Methods: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification., Results: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration., Conclusions: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. Lesser known complications inherent to SSc, such as malignancies and osteoporosis, can lead to decreased quality of life and increased morbidity and mortality. Patients with SSc have a greater risk of developing malignancies than the general population. In addition, they are more likely to be vitamin D deficient and are at great risk of osteoporosis-related fractures. However, these complications can be addressed through preventative measures. The purpose of this review is to provide clinicians with an approach to bone health and cancer screening in SSc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. There are multiple complications inherent to SSc and its management. One of these complications is increased infection risk, which can lead to decreased quality of life and increased morbidity and mortality. Patients with SSc have lower vaccination rates and decreased vaccine seroconversion secondary to immunosuppressive medications compared with the general population. The purpose of this review is to provide clinicians with an approach to vaccinations in SSc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Given the poor treatment options for pulmonary arterial hypertension associated systemic sclerosis (SSc-PAH) patients, we sought to determine clinical safety and efficacy of Dimethylfumarate (DMF), an Nrf2 agonist, and the effects on biomarkers of oxidative stress on SSc-PAH in an exploratory interventional clinical trial., Objectives: The primary objectives were to assess the safety and efficacy of treatment with DMF in patients with SSc-PAH., Methods: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial conducted at two sites in the United States. The primary safety endpoint was the incidence of serious adverse events (SAEs) and all adverse events (AEs) in DMF compared to placebo-treated patients. The primary efficacy endpoint was the change in 6MWD from baseline to the end of treatment at Week 24 in DMF compared to placebo-treated patients., Results: Six participants were randomized to either placebo (n = 2) or DMF (n = 4). Baseline demographics were similar in both groups. A total of 25 adverse events (AEs) occurred in 6 subjects, with 14 AEs (56.0%) having occurred in DMF-treated subjects. 3 occurrences were identified as nausea AEs, and two participants withdrew due to nausea. One participant in the placebo group was withdrawn after a hospitalization SAE due to worsening of heart failure and shortness of breath secondary to anemia. One participant in each group completed protocol. Subjects in the DMF-treated group showed a non-significant reduced decline in 6MWD (relative mean change of -7.07%) from baseline to Week 24 as compared to placebo-treated subjects (relative mean change of -14.97%)., Conclusion: Patients treated for SSc-PAH with 2 and 3-drug regimens, as is now typical for these patients, tolerate DMF poorly. Our small samples size did not provide power to suggest efficacy. We suggest that Nrf2 is still a valid therapeutic target for future trials, using better tolerated Nrf2 agonists.

Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by vasculopathy, fibrosis and immune system activation. Pulmonary hypertension and interstitial lung disease account for majority of SSc-related deaths. Diagnosis of SSc-PAH can be challenging due to nonspecific clinical presentation which can lead to delayed diagnosis. Many screening algorithms have been developed to detect SSc-associated pulmonary arterial hypertension (SSc-PAH) in early stages. Currently used PAH-specific medications are largely extrapolated from IPAH studies due to smaller number of patients with SSc-PAH. In this review, we discuss the current state of knowledge in epidemiology and risk factors for development of SSc-PAH, and challenges and potential solutions in the diagnosis, screening and management of SSc-PAH., Competing Interests: Robyn T Domsic is a consultant for Eicos Sciences. The authors report no other conflicts of interest in this work., (© 2019 Saygin and Domsic.)

Objectives: The patient perspective captured using Patient-Reported Outcome (PRO) instruments provide insight into the patient condition not always captured by physician-derived assessment tools. Target patient population involvement is an essential component of PRO instrument development. We have reviewed the level of patient involvement in the development of PRO instruments used in the assessment of systemic sclerosis (SSc)., Methods: A comprehensive literature review was undertaken to identify studies reporting PRO instruments in SSc. Studies were assessed to establish whether the PRO instruments had been developed specifically for SSc or adopted from other disease areas. Studies reporting PRO instruments specific for SSc were scrutinised for evidence of target patient population involvement in the development of the instrument., Results: A total of 58 PRO instruments that have been used in SSc research were identified. Twelve (21%) of these were developed specifically for outcome assessment within SSc populations. Of these, 5 (42%) had not reported any patient involvement in the development phase of the instrument. Five SSc PRO instruments (42%) involved target patient population in the domain/item generation stage. Four (33%) of SSc PRO instruments had undertaken cognitive interviewing to ensure item wording adequately captured the intended conceptual framework., Conclusions: The majority of PRO instruments used to assess SSc have not involved significant target patient involvement in their development. By involving patients in the development of novel PRO instruments in SSc, we can ensure such instruments adequately capture the experiences most relevant to our patients.

Objectives: To assess the utility of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) in detecting and monitoring pulmonary hypertension (PH) in systemic sclerosis (SSc)., Methods: PHAROS is a multicenter prospective cohort of SSc patients at high risk for developing pulmonary arterial hypertension (SSc-AR-PAH) or with a definitive diagnosis of SSc-PH. We evaluated 1) the sensitivity and specificity of BNP≥64 and NT-proBNP≥210 pg/mL for the detection of SSc-PAH and/ or SSc-PH in the SSc-AR-PAH population; 2) baseline and longitudinal BNP and NT-proBNP levels as predictors of progression to SSc-PAH and/or SSc-PH; 3) baseline BNP≥180, NT-proBNP≥553 pg/mL, and longitudinal changes in BNP and NT-proBNP as predictors of mortality in SSc-PH diagnosed patients., Results: 172 SSc-PH and 157 SSc-AR- PAH patients had natriuretic peptide levels available. Median BNP and NT-proBNP were significantly higher in the SSc-PH versus SSc-AR-PAH group. The sensitivity and specificity for SSc-PAH detection using baseline BNP≥64 pg/mL was 71% and 59%; and for NT-proBNP≥210 pg/mL, 73% and 78%. NT-proBNP showed stronger correlations with haemodynamic indicators of right ventricular dysfunction than BNP. Baseline creatinine, RVSP > 40 mmHg, and FVC%:DLco% ratio ≥1.8 were associated with progression from SSc-AR-PAH to SSc-PH but no association with individual or combined baseline BNP and NT-proBNP levels was observed. Baseline and follow-up BNP or NT-proBNP levels were not predictive of death, however, a composite BNP/NT-proBNP group predicted mortality (HR 3.81 (2.08-6.99), p<.0001)., Conclusions: NT-proBNP may be more useful than BNP in the detection and monitoring of PAH in SSc patients, but additional studies are necessary.

Background: Sublingual frenulum abnormalities have been observed in systemic sclerosis (SSc), but the clinical significance of such features is not known. The goal of this project was to devise a reliable bedside tool to confirm the presence of sublingual frenulum abnormalities in SSc and explore potential associations with patient demographics and gastrointestinal clinical phenotype., Methods: A working group was created to develop a semiquantitative assessment tool for assessing sublingual abnormalities, the Sublingual Abnormalities Index (SAI). Sublingual frenulum thickness, frenulum length, sublingual buccal mucosa pallor, and the presence of oral telangiectasia were each individually scored using 0- to 2-point Likert scales and a composite score of the 4 domains created by summation of the individual scores. Assessment of the sublingual region of 21 patients with SSc and 8 control subjects was undertaken. An image of the sublingual frenulum was obtained using prespecified camera settings to allow assessment of interrater reliability with 2 independent blinded assessors., Results: Scores for each of the SAI domains differed between control subject and SSc population (P = 0.0003). Patients with SSc had a composite SAI score of 4.3 (SD, 0.37). None of the control subjects had a composite SAI score of more than 2. There was excellent interrater reliability between clinician assessment and each blinded assessor (Cohen κ's of 0.72 and 0.82, respectively)., Conclusions: This feasibility study confirms the presence of clinical sublingual abnormalities in SSc, which can be categorized using a simple scoring chart with moderate to near-perfect interrater agreement. The functional significance and pathogenesis of this abnormality warrant further study.

Diffuse systemic sclerosis carries a high morbidity and mortality. The Prospective Registry of Early Systemic Sclerosis (PRESS), a multicentre incident cohort study of patients with early diffuse cutaneous systemic sclerosis, has the goal of advancing the understanding of disease pathogenesis and identifying novel biomarkers. In this review, PRESS investigators discuss the evidence pertaining to the more commonly used treatments for early diffuse SSc skin disease including methotrexate, mycophenolate, cyclophosphamide, azathioprine, and intravenous immunoglobulin. This review highlights the unmet need for effective treatment in early diffuse SSc as well as its more rigorous study. Nonetheless, the PRESS investigators aim to decrease intra- and inter-institutional variability in prescribing in order to improve the understanding of the clinical course of early diffuse SSc skin disease.

Objectives: To compare systemic sclerosis (SSc) patients with and without anti-PM-Scl antibody., Methods: We reviewed the medical records of 76 anti-PM-Scl antibody positive SSc patients and 2349 anti-PMScl negative SSc patients first evaluated during 1980-2004. Patients were included if they had a clinical diagnosis of SSc either alone or in overlap with another connective tissue disease. Anti-PM-Scl antibody was screened for by indirect immunofluorescence and tested by Ouchterlony double immunodiffusion., Results: Anti-PM-Scl antibody positive patients had a significantly higher frequency of a positive ANA with nucleolar staining (87% vs. 32%, p<0.0001) and were younger at both symptom onset (p=0.004) and first physician diagnosis of SSc (p<0.001). They were classified more often as having overlap with another connective tissue disease, particularly polymyositis-dermatomyositis, and more frequently had limited cutaneous involvement (72% vs. 52%, p=0.001). Maximal skin thickening was less in anti-PM-Scl antibody patients (mean modified Rodnan total skin score 6.0±6.3 vs. 15.9±14.2, p<0.001). Anti-PM-Scl antibody positive patients less frequently had peripheral vascular (91% vs. 98%, p=0.0002) and gastrointestinal (52% vs. 79%, p=0.0001) disease. Lung involvement overall had a similar distribution between both groups. However, radiographic evidence of pulmonary fibrosis was more frequent in anti-PM-Scl antibody positive patients (50% vs. 37%, p=0.05) and pulmonary arterial hypertension was less often detected (5% vs. 15%, p<0.04). Skeletal muscle involvement (51% vs. 14%, p<0.0001) and subcutaneous calcinosis (p<0.003) were both significantly more often observed in anti-PM-Scl antibody positive patients. Joint, heart, and kidney involvement were similar in both groups. Overall survival was significantly better for anti-PM-Scl antibody positive patients (10 year cumulative survival rate 91% vs. 65%, p=0.0002). After adjustment for age, sex and limited vs. diffuse cutaneous involvement, patients with anti-PM-Scl antibody were significantly less likely to die (HR=0.32, 95% CI, [0.14, 0.72] p=0.006)., Conclusions: SSc patients with anti-PM-Scl antibody are younger and significantly more often have limited cutaneous involvement, skeletal muscle disease, pulmonary fibrosis and calcinosis compared to anti-PM-Scl antibody negative SSc patients. Ten-year cumulative survival is significantly better in anti-PM-Scl antibody positive SSc patients.

Objectives: To determine the reliability and validity of a new measure of finger motion in patients with systemic sclerosis (SSc), the 'delta finger-topalm' (delta FTP) and compare its psychometric properties to the traditional measure of finger motion, the finger-topalm (FTP)., Methods: Phase 1: The reliability of the delta FTP and FTP were examined in 39 patients with SSc. Phase 2: Criterion and convergent construct validity of both measures were examined in 17 patients with SSc by comparing them to other clinical measures: Total Active Range of Motion (TAROM), Hand Mobility in Scleroderma (HAMIS), the Duruoz Hand Index (DHI), Health Assessment Questionnaire (HAQ), and modified Rodnan skin score (mRSS). Phase 3: Sensitivity to change of the delta FTP was investigated in 24 patients with early diffuse cutaneous SSc., Results: Both measures had excellent intra-rater and inter-rater reliability (ICC 0.92 to 0.99). Fair to strong correlations (rs=0.49-0.94) were observed between the delta FTP and TAROM, HAMIS, and DHI. Fair to moderate correlations were observed between delta FTP and HAQ components related to hand function and upper extremity mRSS. Correlations of the traditional FTP with these measures were fair to strong, but most often the delta FTP outperformed the FTP. The effect size and standardised response mean for the mean delta FTP were 0.50 and 1.10 respectively, over a 2-8 month period., Conclusions: The delta FTP is a valid and reliable measure of finger motion in patients with SSc which outperforms the FTP.