The BILAG-2004 index is associated with development of new damage in SLE.

OBJECTIVE: To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. METHODS: This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. RESULTS: A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. CONCLUSIONS: BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.

A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS).

OBJECTIVES: Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. METHODS: PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. RESULTS: Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI: -0.29, 0.10), P = 0.254, and in mRSS -3.90 (97.5% CI: -8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. CONCLUSION: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

OBJECTIVES: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. METHODS: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. RESULTS: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. CONCLUSION: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.

Estimation of the burden of shielding among a cross-section of patients attending rheumatology clinics with SLE-data from the BSR audit of systemic lupus erythematosus.

OBJECTIVES: We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice. METHODS: We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group. RESULTS: The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9-3.4) times more likely to be in the shielding group than people with no previous LN (P < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3-2.8) and Asian 1.9 (1.3-2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN. CONCLUSION: Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding.

BSR guideline on the management of adults with systemic lupus erythematosus (SLE) 2018: baseline multi-centre audit in the UK.

OBJECTIVES: To assess the baseline care provided to patients with SLE attending UK Rheumatology units, audited against standards derived from the recently published BSR guideline for the management of adults with SLE, the NICE technology appraisal for belimumab, and NHS England's clinical commissioning policy for rituximab. METHODS: SLE cases attending outpatient clinics during any 4-week period between February and June 2018 were retrospectively audited to assess care at the preceding visit. The effect of clinical environment (general vs dedicated CTD/vasculitis clinic and specialized vs non-specialized centre) were tested. Bonferroni's correction was applied to the significance level. RESULTS: Fifty-one units participated. We audited 1021 episodes of care in 1003 patients (median age 48 years, 74% diagnosed >5 years ago). Despite this disease duration, 286 (28.5%) patients had active disease. Overall in 497 (49%) clinic visits, it was recorded that the patient was receiving prednisolone, including in 28.5% of visits where disease was assessed as inactive. Low documented compliance (<60% clinic visits) was identified for audit standards relating to formal disease-activity assessment, reduction of drug-related toxicity and protection against comorbidities and damage. Compared with general clinics, dedicated clinics had higher compliance with standards for appropriate urine protein quantification (85.1% vs 78.1%, P ≤ 0.001). Specialized centres had higher compliance with BILAG Biologics Register recruitment (89.4% vs 44.4%, P ≤ 0.001) and blood pressure recording (95.3% vs 84.1%). CONCLUSIONS: This audit highlights significant unmet need for better disease control and reduction in corticosteroid toxicity and is an opportunity to improve compliance with national guidelines. Higher performance with nephritis screening in dedicated clinics supports wider adoption of this service-delivery model.

A new MHC-linked susceptibility locus for primary Sjögren's syndrome: MICA.

The association of primary Sjögren's syndrome (pSS) with Major Histocompatibility Complex (MHC) alleles is quintessential of MHC-disease associations. Indeed, although disease associations with classical HLA class I and II alleles/haplotypes are amply documented, further dissection is often prevented by the strong linkage disequilibrium across the entire MHC complex. Here we study the association of pSS, not with HLA genes, but with the non-conventional MHC encoded class I gene, MICA (MHC class I chain-related gene A). MICA is selectively expressed within epithelia, and is the major ligand for the activatory receptor, NKG2D, both attributes relevant to pSS' etiology. MICA-pSS association was studied in two independent (French and UK) cohorts representing a total of 959 cases and 1,043 controls. MICA*008 allele was shown to be significantly associated with pSS (pcor=2.61 × 10-35). A multivariate logistic regression showed that this association was independent of all major known MHC-linked risk loci/alleles, as well as other relevant candidate loci that are in linkage disequilibrium with MICA*008 i.e. HLA-B*08:01, rs3131619 (T), MICB*008, TNF308A, HLA-DRB1*03:01 and HLA-DRB1*15:01 (P = 1.84 × 10-04). Furthermore, independently of the MICA*008 allele, higher levels of soluble MICA proteins were detected in sera of pSS patients compared to healthy controls. This study hence defines MICA as a new, MHC-linked, yet HLA-independent, pSS risk locus and opens a new front in our understanding of the still enigmatic pathophysiology of this disease. The fact that the soluble MICA protein is further amplified in MICA*008 carrying individuals, might also be relevant in other auto-immune diseases and cancer.

Systemic interferon type I and type II signatures in primary Sjögren's syndrome reveal differences in biological disease activity.

Objective: To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS). Methods: RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed. Results: Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjögren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time. Conclusions: Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.

Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register.

Objectives: To describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use. Methods: Patients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months. Results: Two hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5-20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10-23) at baseline and 3 (2-12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5-12) to 4 (0-7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5-12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049). Conclusion: RTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.

Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

OBJECTIVE: To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. CONCLUSION: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.

Consensus best practice pathway of the UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis.

OBJECTIVE: Digital vasculopathy (comprising RP, digital ulceration and critical digital ischaemia) is responsible for much of the pain and disability experienced by patients with SSc. However, there is a limited evidence base to guide clinicians in the management of SSc-related digital vasculopathy. Our aim was to produce recommendations that would be helpful for clinicians, especially for those managing patients outside specialist centres. METHODS: The UK Scleroderma Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including digital vasculopathy. RESULTS: This overview presents the background and best practice consensus pathways for SSc-related RP, digital ulceration and critical ischaemia. Examples of drug therapies, including doses, are suggested in order to inform prescribing practice. CONCLUSION: A number of treatment algorithms are provided that are intended to provide the clinician with accessible reference tools for use in daily management.

Second-line agents in myositis: 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids.

OBJECTIVE: Ciclosporin and MTX are used in idiopathic inflammatory myopathies (DM and PM) when patients incompletely respond to glucocorticoids. Their effectiveness is unproved in randomized controlled trials (RCTs). We evaluated their benefits in a placebo-controlled factorial RCT. METHODS: A 56-week multicentre factorial-design double-blind placebo-controlled RCT compared steroids alone, MTX (15-25 mg weekly) plus steroids, ciclosporin (1-5 mg/kg/day) plus steroids and all three treatments. It enrolled adults with myositis (by Bohan and Peter criteria) with active disease receiving corticosteroids. RESULTS: A total of 359 patients were screened and 58 randomized. Of the latter, 37 patients completed 12 months of treatment, 7 were lost to follow-up and 14 discontinued treatment. Patients completing 12 months of treatment showed significant improvement (P < 0.001 on paired t-tests) in manual muscle testing (14% change), walking time (22% change) and function (9% change). Intention to treat and completer analyses indicated that ciclosporin monotherapy, MTX monotherapy and ciclosporin/MTX combination therapy showed no significant treatment effects in comparison with placebo. CONCLUSION: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.

Do the EULAR Sjögren's syndrome outcome measures correlate with health status in primary Sjögren's syndrome?

OBJECTIVE: This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS: Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearman's rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS: This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION: This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.

Health-related utility values of patients with primary Sjögren's syndrome and its predictors.

OBJECTIVES: EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögren's syndrome (PSS) in the UK. METHODS: Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. RESULTS: The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587-0.796, range -0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. CONCLUSIONS: This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Novel photoplethysmography cardiovascular assessments in patients with Raynaud's phenomenon and systemic sclerosis: a pilot study.

OBJECTIVE: Multisite photoplethysmography (PPG) cardiovascular assessments can evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of this pilot study was to investigate the potential clinical utility of the technology in assessing patients with SSc and primary RP (PRP). METHODS: Multisite PPG pulse measurements, a reference ankle brachial pressure index (ABPI) and a full clinical assessment were undertaken for three subject groups: SSc, PRP and controls. Endothelial and autonomic function and arterial disease measures were obtained using pulse wave analysis. RESULTS: Nineteen SSc, 19 PRP and 23 control subjects were assessed and compared. Endothelial function was significantly impaired in SSc (P < 0.02), but with no difference between controls and PRP. Receiver operating characteristic-based classification accuracy was 81% (sensitivity 90%, specificity 74%) for separating SSc from controls and 82% (sensitivity 84%, specificity 79%) for separating SSc from PRP. SSc patients with digital ulcers had significantly lower endothelial function compared with those without ulcers (P < 0.05). Autonomic dysfunction was suggested in both SSc and PRP and was most exaggerated in patients with diffuse SSc. All groups had overall normal ABPI and arterial stiffness timing measures. Bilateral timing differences at the toes, which represents peripheral occlusive arterial disease, did show increased asymmetry in SSc (P < 0.02). CONCLUSION: Multisite PPG pulse technology showed potential diagnostic ability. By using measures of endothelial function, it differentiated SSc from control and PRP subjects with an accuracy of at least 81%. Objective pulse-derived measures of autonomic function and arterial disease in SSc have also been reported in this pilot study.