Step forward in early recognition of systemic sclerosis: data from the Leiden CCISS cohort.

BACKGROUND: Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study evaluated whether early recognition of SSc has improved over time and whether disease characteristics and survival has changed over time. METHODS: 643 SSc patients fulfilling American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria were included and categorised into three groups based on cohort-entry year: (1) 2010-2013 (n=229 (36%)), (2) 2014-2017 (n=207 (32%)) and (3) 2018-2021 (n=207 (32%)). Variables including disease duration, interstitial lung disease (ILD), digital ulcers (DU), diffuse cutaneous SSc (dcSSc), antitopoisomerase (ATA) and anticentromere (ACA) antibodies, and survival from disease onset were compared between cohort-entry groups, including analyses stratified for sex and autoantibodies. RESULTS: Over time, duration between onset of disease symptoms and cohort entry decreased in males and females, but was always longer in females than in males.The proportion of patients presenting with DU decreased, especially in ACA+SSc patients. Almost no ACA+ patients presented with ILD, while in ATA+ patients this proportion was 25% in 2010-2013 and decreased to 19% in 2018-2021. A reduction in patients presenting with clinically meaningful ILD and dcSSc was observed.Overall 8-year survival for males was 59% (95% CI 40% to 73%) and for females 89% (95% CI 82% to 93%). Eight-year survival showed a trend for improvement over time, and was always worse in males. CONCLUSION: We observed a decrease in disease duration in Leiden CCISS cohort at cohort entry, possibly indicating more timely diagnosis of SSc. This could provide opportunities for early interventions. While symptom duration at presentation is longer in females, mortality is consistently higher in males, underlining the urge for sex-specific treatment and follow-up.

The Natural Sequence in Which Subclinical Inflamed Joint Tissues Subside or Progress to Rheumatoid Arthritis: A Study of Serial MRIs in the TREAT EARLIER Trial.

OBJECTIVE: The natural trajectory of clinical arthritis progression at the tissue level remains elusive. We hypothesized that subclinical inflammation in different joint tissues (synovitis, tenosynovitis, osteitis) increases in a distinct temporal order in patients with clinically suspect arthralgia (CSA) who develop rheumatoid arthritis (RA) and subsides in a different sequence when CSA spontaneously resolves. METHODS: We studied 185 serial magnetic resonance images (MRIs) from CSA patients with subclinical joint inflammation from the placebo arm of the TREAT EARLIER trial: 52 MRIs from 21 RA progressors (MRIs conducted at 1 year before, at 4 months before, and upon RA development), and 133 MRIs from 35 patients with spontaneous resolution of pain (MRIs conducted at baseline and at 4, 12, and 24 months). MRIs were scored for osteitis, synovitis, and tenosynovitis. We used cross-lagged models to evaluate 2 types of time patterns between pairs of inflamed tissues: a simultaneous pattern (coinciding changes) and a subsequent pattern (inflammatory changes in 1 tissue preceding changes in another tissue). RESULTS: In patients who developed RA, synovitis, tenosynovitis, and osteitis increased simultaneously. Increasing osteitis occurred in the final 4 months before RA diagnosis, following incremental tenosynovitis and synovitis changes during the 1 year to 4 months before diagnosis (P < 0.01). In anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative patients who progressed to RA, osteitis increased just before RA development. In patients with pain resolution, simultaneous decreases in synovitis, tenosynovitis, and osteitis occurred, with tenosynovitis decreasing in the first 4 months after CSA onset preceding decreasing synovitis and osteitis during 4-12 months (P = 0.02 and P < 0.01). CONCLUSION: We identified natural sequences of subclinical inflammation in different joint tissues, which deepens our understanding of clinical arthritis and RA development. During RA progression, increasing osteitis followed previous increases in tenosynovitis and synovitis. During pain resolution, tenosynovitis decreased first, followed by decreasing synovitis and osteitis.

Randomized feasibility trial of the Scleroderma Patient-centered Intervention Network hand exercise program (SPIN-HAND).

Purpose: The Scleroderma Patient-centered Intervention Network (SPIN) online hand exercise program (SPIN-HAND), is an online self-help program of hand exercises designed to improve hand function for people with scleroderma. The objective of this feasibility trial was to evaluate aspects of feasibility for conducting a full-scale randomized controlled trial of the SPIN-HAND program. Materials and Methods: The feasibility trial was embedded in the SPIN cohort and utilized the cohort multiple randomized controlled trial (cmRCT) design. In the cmRCT design, at the time of cohort enrollment, cohort participants consent to be assessed for trial eligibility and randomized prior to being informed about trials conducted using the cohort. When trials were conducted in the cohort, participants randomized to the intervention were informed and consented to access the intervention. Participants randomized to control were not informed that they have not received an intervention. All participants eligible and randomized to participate in the trial were included in analyses on an intent-to-treat basis. Cohort participants with a Cochin Hand Function Scale score ≥ 3/90 and an interest in using an online hand-exercise intervention were randomized (1:1 ratio) to be offered as usual care plus the SPIN-HAND Program or usual care for 3 months. User satisfaction was assessed with semi-structured interviews. Results: Of the 40 randomized participants, 24 were allocated to SPIN-HAND and 16 to usual care. Of 24 participants randomized to be offered SPIN-HAND, 15 (63%) consented to use the program. Usage of SPIN-HAND content among the 15 participants who consented to use the program was low; only five (33%) logged in more than twice. Participants found the content relevant and easy to understand (satisfaction rating 8.5/10, N = 6). Automated eligibility and randomization procedures via the SPIN Cohort platform functioned properly. The required technical support was minimal. Conclusions: Trial methodology functioned as designed, and the SPIN-HAND Program was feasibly delivered; however, the acceptance of the offer and use of program content among accepters were low. Adjustments to information provided to potential participants will be implemented in the full-scale SPIN-HAND trial to attempt to increase offer acceptance.

Evolution of Systemic Sclerosis-Associated Interstitial Lung Disease One Year After Hematopoietic Stem Cell Transplantation or Cyclophosphamide.

OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc-ILD in SSc patients treated with HSCT (assessed by high-resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction. METHODS: We semiquantitatively scored total ILD extent, reticulations, and ground-glass opacities (GGO) scores at baseline and at the 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between changes in HRCT scores and PFT results and predictors of ILD improvement were studied. RESULTS: We included 51 patients (those treated with HSCT [n = 20] and those treated with CYC [n = 31]). The mean change in total ILD score was -5.1% (95% confidence interval [95% CI] -10.2, 0.0) in the HSCT treatment group (P = 0.050), and -1.0% (95% CI -4.3, 2.3) in the CYC treatment group (P = 0.535). For all patients, the evolution of HRCT scores was weakly associated with relative changes in PFT results. In univariate logistic regression, higher ground-glass opacities, higher total ILD, and lower single-breath diffusing capacity for carbon monoxide scores at baseline predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors. CONCLUSION: One year after treatment with HSCT, a nonsignificant but clear reduction of SSc-ILD extent was observed. Changes in PFT results were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive.

Evidence and consensus-based recommendations for non-pharmacological treatment of fatigue, hand function loss, Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

OBJECTIVE: SSc is a complex CTD affecting mental and physical health. Fatigue, hand function loss, and RP are the most prevalent disease-specific symptoms of systemic sclerosis. This study aimed to develop consensus and evidence-based recommendations for non-pharmacological treatment of these symptoms. METHODS: A multidisciplinary task force was installed comprising 20 Dutch experts. After agreeing on the method for formulating the recommendations, clinically relevant questions about patient education and treatments were inventoried. During a face-to-face task force meeting, draft recommendations were generated through a systematically structured discussion, following the nominal group technique. To support the recommendations, an extensive literature search was conducted in MEDLINE and six other databases until September 2020, and 20 key systematic reviews, randomized controlled trials, and published recommendations were selected. Moreover, 13 Dutch medical specialists were consulted on non-pharmacological advice regarding RP and digital ulcers. For each recommendation, the level of evidence and the level of agreement was determined. RESULTS: Forty-one evidence and consensus-based recommendations were developed, and 34, concerning treatments and patient education of fatigue, hand function loss, and RP/digital ulcers-related problems, were approved by the task force. CONCLUSIONS: These 34 recommendations provide guidance on non-pharmacological treatment of three of the most frequently described symptoms in patients with systemic sclerosis. The proposed recommendations can guide referrals to health professionals, inform the content of non-pharmacological interventions, and can be used in the development of national and international postgraduate educational offerings.

How do patients with systemic sclerosis experience currently provided healthcare and how should we measure its quality?

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.

Pulmonary Vascular Morphology Associated With Gas Exchange in Systemic Sclerosis Without Lung Fibrosis.

PURPOSE: Gas exchange in systemic sclerosis (SSc) is known to be affected by fibrotic changes in the pulmonary parenchyma. However, SSc patients without detectable fibrosis can still have impaired gas transfer. We aim to investigate whether pulmonary vascular changes could partly explain a reduction in gas transfer of SSc patients without fibrosis. MATERIALS AND METHODS: We selected 77 patients whose visual computed tomography (CT) scoring showed no fibrosis. Pulmonary vessels were detected automatically in CT images, and their local radii were calculated. The frequency of occurrence for each radius was calculated, and, from this radius histogram, 2 imaging biomarkers (α and ß) were extracted, wherein α reflects the relative contribution of small vessels compared with large vessels, and ß represents the vessel tree capacity. Correlations between imaging biomarkers and gas transfer [single-breath diffusion capacity for carbon monoxide corrected for hemoglobin concentration (DLCOc) %predicted] were evaluated with Spearman correlation. Multivariable stepwise linear regression was performed with DLCOc %predicted as the dependent variable and age, BMI, sPAP, FEV1 %predicted, TLC %predicted, FVC %predicted, α, ß, voxel size, and CT-derived lung volume as independent variables. RESULTS: Both α and ß were significantly correlated with gas transfer (R=-0.29, P-value=0.011 and R=0.32, P-value=0.004, respectively). The multivariable stepwise linear regression analysis selected sPAP [coefficient=-0.78; 95% confidence interval (CI)=-1.07, -0.49; P-value<0.001], ß (coefficient=8.6; 95% CI=4.07, 13.1; P-value<0.001), and FEV1% predicted (coefficient=0.3; 95% CI=0.12, 0.48; P-value=0.001) as significant independent predictors of DLCOc %predicted (R=0.71, P-value<0.001). CONCLUSIONS: In SSc patients without detectable pulmonary fibrosis, impaired gas exchange is associated with alterations in pulmonary vascular morphology.

The association of sociodemographic and disease variables with hand function: a Scleroderma Patient-centered Intervention Network cohort study.

OBJECTIVES: Impaired hand function in systemic sclerosis (SSc) is a primary cause of disability and contributes diminished health-related quality of life. The objective of the present study was to evaluate sociodemographic, lifestyle, and disease-related factors independently associated with hand function in SSc. METHODS: Patients enrolled in the Scleroderma Patient-centered Intervention Network Cohort who completed baseline study questionnaires between March 2014 and September 2017 were included. Hand function was measured using the Cochin Hand Function Scale (CHFS). Multiple linear regression analysis was used to identify independent correlates of impaired hand function. RESULTS: Among 1193 participants (88% female), the mean CHFS score was 13.3 (SD=16.1). Female sex (standardised regression coefficient, beta (ß)=.05), current smoking (ß=.07), higher BMI (ß=.06), diffuse SSc (ß=0.14), more severe Raynaud's scores (ß=.23), more severe finger ulcer scores (ß=.23), moderate (ß=0.19) or severe small joint contractures (ß=.20), rheumatoid arthritis (ß=0.07), and idiopathic inflammatory myositis (ß=0.06) were significantly associated with higher CHFS scores (more impaired hand function). Consumption of 1-7 alcoholic drinks per week (ß=-0.07) was associated with lower CHFS scores (less impaired hand function) compared to no drinking. CONCLUSIONS: Multiple factors are associated with hand function in SSc. The presence of moderate or severe small joint contractures, the presence of digital ulcers, and severity of Raynaud's phenomenon had the largest associations. Effective interventions are needed to improve the management of hand function in patients with SSc.

Randomized feasibility trial of the Scleroderma Patient-centered Intervention Network hand exercise program (SPIN-HAND): Study protocol.

Background: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. Design and methods: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. Discussion: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. Trial registration: ClinicalTrials.gov Identifier: NCT03092024.

Exercise habits and factors associated with exercise in systemic sclerosis: a Scleroderma Patient-centered Intervention Network (SPIN) cohort study.

OBJECTIVE: Exercise is associated with improved health in many medical conditions. Little is known about the exercise habits of people with systemic sclerosis (SSc, or scleroderma). This study assessed the proportion of individuals with SSc who exercise and associations of demographic and disease variables with exercise. Additionally, the weekly amount of time spent exercising and the types of exercise performed were assessed among patients exercising. METHODS: The sample consisted of adult participants with SSc enrolled in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort who completed baseline questionnaires from March 2014 through August 2015. Baseline questionnaires included questions on exercise habits, physician-reported medical characteristics, self-report demographic characteristics, the Health Assessment Questionnaire-Disability Index, Patient Health Questionnaire-9, and Patient-Reported Outcomes Measurement Information System-29. RESULTS: Of 752 patients, 389 (51.7%) reported presently engaging in exercise, and these patients exercised on average 4.7 h [standard deviation (SD) = 2.8] per week. Among patients who reported exercising, walking was most commonly reported (n = 295, 75.8%). In bivariate analyses, present exercise was associated with more education, lower body mass index, some (versus no) alcohol consumption, non-smoking, limited/sine disease subtype, absence of skin thickening, lower disability, higher physical function, lower symptoms of anxiety and depression, less fatigue, lower sleep disturbance, higher ability to participate in social roles and activities, and less pain. CONCLUSIONS: Approximately half of SSc patients reported that they are currently exercising with walking being the most common form of exercise. Understanding exercise patterns and factors associated with exercise will help better inform intervention programs to support exercise for patients with SSc. Implications for rehabilitation Systemic sclerosis is a rare autoimmune rheumatic disease associated with great morbidity and highly diverse presentation. Approximately half of people with both limited and diffuse systemic sclerosis report exercising. Most exercisers walk, but patients engage in a wide variety of exercise-related activities. Individually designed exercise programs are most likely to support and encourage exercise in patients with diverse disease manifestations.

Lung Density and Pulmonary Artery Diameter are Predictors of Pulmonary Hypertension in Systemic Sclerosis.

PURPOSE: The aim was to evaluate computed tomography (CT)-measured pulmonary artery diameter (PAD) and lung density as predictors of pulmonary hypertension (PH) in subjects with systemic sclerosis (SSc). We compared these PAD values with normal values and between SSc subgroups with PH and/or interstitial lung disease (ILD). We investigated whether PAD predicts PH and whether lung densitometry, by using the 85th percentile density value (Perc85) as a measure for ILD, can predict PH. MATERIALS AND METHODS: PAD and Perc85 were measured in axial CT scans and compared between 54 SSc and 76 control subjects. Four SSc subgroups were defined on the basis of PH (systolic PA pressure ≥35 mm Hg) and/or ILD (fibrosis score ≥7): PH-/ILD-, PH-/ILD+, PH+/ILD-, and PH+/ILD+. The association of PAD with age, body mass index, Perc85, lung function, and hemodynamic measures was investigated using univariate correlation along with the predictive value of these measures with respect to PH. RESULTS: PAD in SSc was larger than that in controls (30.1±4.9 vs. 26.9±2.7 mm, P<0.001). PH+ patients showed increased PAD compared with PH- patients (34.2±4.2 vs. 28.6±4.3 mm, P<0.001), where PH+/ILD+ subjects showed the widest diameter (34.6±4.1 mm). In SSc patients, hemodynamic measures, age, body mass index, Perc85, and lung function correlated with PAD. PAD was best explained by Perc85, together with age (R=0.358). PAD best predicted PH (AUC, 0.877; P<0.001), and PAD≥30.7 mm showed 80% sensitivity and 87% specificity. Perc85 also predicted PH (AUC, 0.733; P=0.024). CONCLUSIONS: In subjects with SSc, lung density and PAD are CT markers, each with predictive value for PH.

Predicting cardiopulmonary involvement in patients with systemic sclerosis: complementary value of nailfold videocapillaroscopy patterns and disease-specific autoantibodies.

Objective: To evaluate the prevalence of anti-extractable nuclear antigen (anti-ENA) antibodies in Dutch SSc patients and the predictive power of the combination of specific anti-ENA antibodies and nailfold videocapillaroscopy (NVC) patterns to improve identification of patients with high risk for cardiopulmonary involvement. Methods: A total of 287 patients (79%) from the Leiden SSc-Cohort had data available on NVC-pattern (no SSc-specific, early, active, late) and anti-ENA antibodies. Associations between anti-ENA/NVC combinations with cardiopulmonary parameters were explored using logistic regression. Results: Prevalence of ACA was 37%, anti-Scl-70 24%, anti-RNP 9%, anti-RNAPIII 5%, anti-fibrillarin 4%, anti-Pm/Scl 3%, anti-Th/To 0.3% and anti-Ku 1.4%. NVC showed a SSc-specific pattern in 88%: 10% early, 42% active and 36% late. The prevalence of different NVC patterns was equally distributed among specific anti-ENA antibodies, except for the absence of early pattern in anti-RNP positive patients. Fifty-one percent had interstitial lung disease (ILD), 59% had decreased diffusion capacity for carbon monoxide and 16% systolic pulmonary artery pressure >35 mmHg (sPAP↑). Regardless of ENA-subtype, NVC-pattern showed a stable association with presence of ILD or sPAP↑. For ILD, the odds ratios (ORs) were 1.3-1.4 ( P < 0.05 for analyses with anti-RNAPIII, anti-RNP). For diffusion capacity for carbon monoxide, the OR was 1.5 ( P < 0.05 for analyses with ACA, anti-Scl-70, anti-RNAPIII, anti-RNP). For sPAP↑, the ORs were 2.2-2.4 ( P < 0.05 for analyses with anti-RNAPIII, anti-RNP). Conclusion: In Dutch SSc patients, all SSc-specific auto-antibodies were found, with ACA and anti-Scl-70 being the most prevalent. Strikingly, the association between NVC-pattern and heart/lung involvement was independent of specific anti-ENA antibodies, which might indicate microangiopathy is an important cause of organ involvement.

Validity and responsiveness of the Michigan Hand Questionnaire in patients with systemic sclerosis.

OBJECTIVE: The aim was to assess the validity and responsiveness of the Michigan Hand Questionnaire (MHQ) in patients with SSc. METHODS: Data were gathered in connection with a randomized, controlled trial comparing the effectiveness of a 12-week multidisciplinary team care programme, including a hand function treatment module, with regular care. Hand function was evaluated by the MHQ (37 items, six domains: Function, Daily activities, Pain, Work, Aesthetics and Satisfaction) and other measurements, including the HAQ, Hand Mobility in Scleroderma, Sequential Occupational Dexterity Assessment (SODA), grip strength, pinch grip and modified Rodnan Skin Score. Fifty-three patients (28 intervention group and 25 control group) completed evaluation at baseline and after 12 weeks. Validity was determined by computing Spearman correlation coefficients between the baseline MHQ total score and subscales and other measures of (hand) disability. Responsiveness in the intervention group was evaluated by the standardized response mean and effect size (ES). In addition, the pooled ES for the difference between the two groups was computed. RESULTS: Significant correlations were seen between the MHQ total score and the HAQ (r = -0.62), Hand Mobility in Scleroderma (r = -0.54), SODA (r = 0.47), SODA Pain (r = 0.32) and modified Rodnan Skin Score (r = 0.46). The ES of the MHQ total score within the intervention group was 0.49, which was larger than that of all other outcome measures. Similar results were obtained for the standardized response mean. The pooled ES of the difference between intervention and control groups for the MHQ total score was 0.86. CONCLUSION: The MHQ demonstrated adequate validity and responsiveness in patients with SSc.

Therapeutic and diagnostic outcomes of a standardised, comprehensive care pathway for patients with systemic sclerosis.

OBJECTIVES: To determine the outcomes, including number of medical interventions and initiation of immunosuppressive treatment of a standardised, comprehensive, diagnostic care pathway for patients with systemic sclerosis (SSc). Patient characteristics associated with need for medical interventions and with need for immunosuppressive treatment were determined. METHODS: Data were routinely gathered in connection with a 2-day care pathway combining multidisciplinary care and complete diagnostic work-up of organ involvement in SSc. The number of patients in whom the pathway resulted in medical interventions, and/or initiation of immunosuppressives was recorded. Patient characteristics and diagnostic tests results were compared between patients with and without medical interventions, and patients with and without initiation of immunosuppressives by means of multivariable logistic regression analyses. RESULTS: During a period of 44 months, 226 patients with SSc were referred to the care pathway. They included 186 (82%) women with mean age of 54 (SD 14.5) years, and median disease duration of 4 years (range 1-11); 73 (32%) of them had diffuse cutaneous SSc. Medical interventions were initiated in 191 (85%) patients, including initiation of immunosuppressive treatment in n=49 (22%). Presence of telangiectasias and higher erythrocyte sedimentation rate were associated with any medical intervention. Of commonly available variables, lower age, higher skin score and absence of anticentromere antibody were associated with initiation of immunosuppressives. CONCLUSIONS: A standardised comprehensive 2-day care pathway for patients with SSc resulted in additional diagnostic or therapeutic interventions in 85% of the patients, regardless of SSc subtype and disease duration. In 22% of the patients, immunosuppressive treatment was initiated.

Using Optimal Test Assembly Methods for Shortening Patient-Reported Outcome Measures: Development and Validation of the Cochin Hand Function Scale-6: A Scleroderma Patient-Centered Intervention Network Cohort Study.

OBJECTIVE: To develop and validate a short form of the Cochin Hand Function Scale (CHFS), which measures hand disability, for use in systemic sclerosis, using objective criteria and reproducible techniques. METHODS: Responses on the 18-item CHFS were obtained from English-speaking patients enrolled in the Scleroderma Patient-Centered Intervention Network Cohort. CHFS unidimensionality was verified using confirmatory factor analysis, and an item response theory model was fit to CHFS items. Optimal test assembly (OTA) methods identified a maximally precise short form for each possible form length between 1 and 17 items. The final short form selected was the form with the least number of items that maintained statistically equivalent convergent validity, compared to the full-length CHFS, with the Health Assessment Questionnaire (HAQ) disability index (DI) and the physical function domain of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29). RESULTS: There were 601 patients included. A 6-item short form of the CHFS (CHFS-6) was selected. The CHFS-6 had a Cronbach's alpha of 0.93. Correlations of the CHFS-6 summed score with HAQ DI (r = 0.79) and PROMIS-29 physical function (r = -0.54) were statistically equivalent to the CHFS (r = 0.81 and r = -0.56). The correlation with the full CHFS was high (r = 0.98). CONCLUSION: The OTA procedure generated a valid short form of the CHFS with minimal loss of information compared to the full-length form. The OTA method used was based on objective, prespecified criteria, but should be further studied for viability as a general procedure for shortening patient-reported outcome measures in health research.

Impact of pulmonary fibrosis and elevated pulmonary pressures on right ventricular function in patients with systemic sclerosis.

OBJECTIVES: Right ventricular (RV) dysfunction is of great prognostic value in patients with SSc. The aim of the present study was to assess in these patients the relationship between pulmonary fibrosis and elevated pulmonary pressure (PHT) with RV function. METHODS: A total of 102 SSc patients who underwent thoracic CT and transthoracic echocardiography were included. Speckle tracking-derived RV free wall strain was used to assess RV function. RESULTS: A total of 51 (50%) SSc patients did not have pulmonary fibrosis or PHT, 32 (31%) patients had pulmonary fibrosis but no PHT and the remaining 19 (19%) patients had both pulmonary fibrosis and PHT. Patients with both pulmonary fibrosis and PHT had the most impaired RV free wall strain [-16.8% (s.d. 3.1)] compared with patients with pulmonary fibrosis and no PHT [-21.5% (s.d. 3.6)] and patients with no pulmonary fibrosis and no PHT [-24.0% (s.d. 4.4)]. All three SSc groups showed impaired RV free wall strain compared with controls [-28.0% (s.d. 4.2)]. Importantly, multivariate regression analysis demonstrated that pulmonary fibrosis and left ventricular ejection fraction were independently associated with impaired RV free wall strain in SSc patients. CONCLUSION: SSc patients show impaired RV function compared with controls. Both pulmonary fibrosis and PHT are independently associated with RV dysfunction.

A prediction model for progressive disease in systemic sclerosis.

OBJECTIVE: To develop a model that assesses the risk for progressive disease in patients with systemic sclerosis (SSc) over the short term, in order to guide clinical management. METHODS: Baseline characteristics and 1 year follow-up results of 163 patients with SSc referred to a multidisciplinary healthcare programme were evaluated. Progressive disease was defined as: death, ≥10% decrease in forced vital capacity, ≥15% decrease in diffusing capacity for carbon monoxide, ≥10% decrease in body weight, ≥30% decrease in estimated-glomerular filtration rate, ≥30% increase in modified Rodnan Skin Score (with Δ≥5) or ≥0.25 increase in Scleroderma Health Assessment Questionnaire. The number of patients with progressive disease was determined. Univariable and multivariable logistic regression analyses were used to assess the probability of progressive disease for each individual patient. Performance of the prediction model was evaluated using a calibration plot and area under the receiver operating characteristic curve. RESULTS: 63 patients had progressive disease, including 8 patients who died ≤18 months after first evaluation. Multivariable analysis showed that friction rubs, proximal muscular weakness and decreased maximum oxygen uptake as % predicted, adjusted for age, gender and use of immunosuppressive therapy at baseline, were significantly associated with progressive disease. Using the prediction model, the predicted chance for progressive disease increased from a pretest chance of 37% to 67-89%. CONCLUSIONS: Using the prediction model, the chance for progressive disease for individual patients could be doubled. Friction rubs, proximal muscular weakness and maximum oxygen uptake as % predicted were identified as relevant parameters.

Effectiveness of Nonpharmacologic Interventions in Systemic Sclerosis: A Systematic Review.

OBJECTIVE: To systematically and comprehensively document the effectiveness of nonpharmacologic interventions on physical functioning and psychological well-being in patients with systemic sclerosis (SSc). METHODS: Multiple electronic databases were searched for studies on the effectiveness of nonpharmacologic interventions in SSc. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), and observational designs (ODs) with ≥10 participants were included. Two reviewers independently assessed methodologic quality using the Downs and Black checklist. RESULTS: Twenty-three studies (9 RCTs, 4 CCTs, and 10 ODs) were included. Studies assessing comparable interventions were grouped, resulting in data for 16 different interventions. The total number of patients included per study ranged from 10 to 53. Seventeen different outcome domains were assessed, with hand function, limitations in activities, and quality of life being assessed most frequently. Three studies, all RCTs, were rated as high quality. These RCTs reported that 1) a multifaceted oral health intervention improves mouth hygiene, and additional orofacial exercises did not improve mouth opening, 2) a multidisciplinary team-care program improves limitations in activities, mouth opening, and hand grip strength, and 3) manual lymph drainage improves hand function, limitations in activities, and quality of life. CONCLUSION: The body of knowledge regarding nonpharmacologic care in SSc is very limited due to the wide variety in studied interventions and outcomes in the relatively uncommon but highly disabling disease. To structure and focus future research, an international consensus should be established to prioritize primary targets for nonpharmacologic treatment and the content of interventions and to agree on a core set of outcome measures.

Lung structure and function relation in systemic sclerosis: application of lung densitometry.

INTRODUCTION: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. MATERIAL AND METHODS: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. RESULTS: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R=-0.49, P=0.001) and FVC %predicted (R=-0.64, P<0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. CONCLUSIONS: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure-function relation in SSc. This provides support for future studies to determine whether structural changes do precede lung function decline.

Determinants of reaching drug-free remission in patients with early rheumatoid or undifferentiated arthritis after one year of remission-steered treatment.

OBJECTIVE: The aim of this study was to assess whether baseline characteristics in patients with undifferentiated arthritis or early RA affect the possibility of achieving drug-free remission after 1 year (DFR1 year) of early remission induction therapy. METHODS: We included 375 patients participating in the IMPROVED study who achieved remission (DAS < 1.6) after 4 months (early remission) and were by protocol able to achieve DFR1 year. Having started with MTX plus prednisone, patients tapered prednisone to zero; after 8 months, those still in remission tapered MTX to zero, while those not in remission restarted prednisone. Characteristics of patients achieving and not achieving DFR1 year were compared. Logistic regression was performed to identify predictors of DFR1 year. RESULTS: After 1 year, 119 patients (32%) were in DFR. Presence of RF, fulfilling the 2010 criteria for RA, and a low tender joint count were associated with achieving DFR1 year, whereas presence of ACPA was not. None of the baseline characteristics was independently associated with DFR1 year. DFR1 year was sustained for 4 months in 65% of the patients. ACPA-positive patients less often had sustained DFR than ACPA-negative patients (58% vs 80%, P = 0.013). CONCLUSION: After 1 year of remission-steered treatment, 32% of the patients who had achieved early remission after 4 months were able to taper medication and achieved DFR. Neither the presence of ACPA nor any other baseline characteristics were independently associated with achieving DFR1 year, but in ACPA-positive patients DFR was less often sustained.