Citations

Objective This study aims to identify factors associated with patient global assessment (PtGA) and physician global assessment (PhGA) and discordance between them in systemic sclerosis (SSc). Methods Data from adults with early SSc (<5 years) from the Collaborative National Quality and Efficacy Registry were included. PtGA and PhGA (0–10 scale), clinical evaluations, and patient‐reported outcomes (PROs) were collected every six months. Multivariable mixed‐effects linear regression identified factors associated with PtGA and PhGA using (1) clinical variables and (2) clinical variables plus PROs. Relative weight analysis (RWA) determined the relative importance of each variable. Discordance (≥2 points between PtGA and PhGA) was assessed using multinomial mixed‐effects logistic regression. Results Among 956 patients (83% women, 33% limited disease), mean PtGA and PhGA at enrollment were 4.2 (SD 2.6) and 3.4 (SD 2.0), respectively ( P < 0.001). RWA of clinical variables identified modified Rodnan skin score (mRSS) and New York Heart Association (NYHA) functional class as most influential for both global assessments. After including PROs, PtGA was most influenced by measures of pain, skin symptoms, and physical function. Discordance occurred in 53% of patients (35% PtGA worse, 18% PhGA worse). Worse PtGA was associated with higher overall pain and discomfort. Worse PhGA was associated with higher mRSS, worse NYHA class, higher pain interference, and lower diffusing capacity of the lung. Conclusion Discordance between PtGA and PhGA occurs commonly, highlighting the need for comprehensive symptom management and measurement of disease burden in this complex disease. In SSc, differences in PtGA and PhGA reflect dissimilar weighting of data elements.

Objective Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts. Methods All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non‐RP symptom. Results In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 (31.1%) of 938 patients had a non‐RP initial symptom, most commonly puffy fingers/hands. Black patients had a non‐RP symptom before RP more commonly than patients in other race and ethnicity categories. Non‐RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA polymerase III antibody positivity. Conclusion In two large US cohorts, >30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the “warning sign” of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc‐associated autoantibodies, including RNA polymerase III.

Our study shows an early increase in kynurenine pathway metabolism in at-risk subjects with systemic sclerosis who develop pulmonary arterial hypertension (PAH). We show that kynurenine pathway upregulation precedes clinical diagnosis and that this metabolic shift is associated with increased disease severity and shorter survival times. We also show that gene expression of TDO2, an enzyme that generates kynurenine from tryptophan, rises with PAH development.

Abstract Objectives SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with &lt;5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. Methods CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0–0.49); moderate (0.50–1.00), and severe-to-very severe (1.01–3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. Results Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. Conclusion This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.

ObjectiveTo determine the independent risk factors for diastolic dysfunction (DD) in patients with systemic sclerosis (SSc) and to evaluate the impact of DD on mortality.MethodsSSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort between November 1, 2006 and November 1, 2017 with ≥1 analyzable 2‐dimensional (2‐D) echocardiogram in our system were included (n = 806). DD risk factors and SSc disease characteristics were prospectively obtained, and the presence or absence of DD was determined using the most recent 2‐D echocardiogram. Logistic regression models examined associations between clinical risk factors and DD, and Cox proportional hazards models were used to assess survival.ResultsDD was present in 18.6% of participants. The majority of participants were female (84%) with a median age of 58.4 years (interquartile range 48.8–68.1). Older age (odds ratio [OR] 1.12 [95% confidence interval (95% CI) 1.09–1.15], P < 0.001), coronary artery disease (OR 3.69 [95% CI 1.52–8.97], P = 0.004), obesity (OR 4.74 [95% CI 2.57–8.74], P < 0.001), longer SSc disease duration (OR 1.04 [95% CI 1.01–1.06], P = 0.004), diffusing capacity for carbon monoxide ≤60% of predicted (OR 2.41 [95% CI 1.40–4.16], P = 0.002), and history of scleroderma renal crisis (OR 3.18 [95% CI 1.12–9.07], P = 0.031) were all independently associated with an increased risk of DD. Anti–Scl‐70 positivity (OR 0.49 [95% CI 0.26–0.93], P = 0.03) and severe gastrointestinal disease (OR 0.48 [95% CI 0.30–0.79], P = 0.004) were associated with a reduced risk of DD. The presence of DD was independently associated with an increase in the risk of mortality (hazard ratio 1.69 [95% CI 1.07–2.68], P = 0.027).ConclusionDD is independently associated with an increased risk of mortality in patients with SSc. Potentially modifiable risk factors, including coronary artery disease and obesity, should be addressed in patients with SSc to reduce mortality risk.