Outcome clusters and their stability over 1 year in patients with SLE: self-reported and performance-based cognitive function, disease activity, mood and health-related quality of life.

OBJECTIVE: To determine if self-reported fatigue, anxiety, depression, cognitive difficulties, health-related quality of life, disease activity scores and neuropsychological battery (NB) cluster into distinct groups in patients with SLE based on symptom intensity and if they change at 1-year follow-up. METHODS: This is a retrospective analysis of consecutive consenting patients, followed at a single centre. Patients completed a comprehensive NB, the Beck Anxiety Inventory, Beck Depression Inventory, Fatigue Severity Scale, Short-Form Health Survey Physical Component Summary and Mental Component Summary scores and the Perceived Deficits Questionnaire. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index 2000. Ward's method was used for clustering and principal component analysis was used to visualise the number of clusters. Stability at 1 year was assessed with kappa statistic. RESULTS: Among 142 patients, three clusters were found: cluster 1 had mild symptom intensity, cluster 2 had moderate symptom intensity and cluster 3 had severe symptom intensity. At 1-year follow-up, 49% of patients remained in their baseline cluster. The mild cluster had the highest stability (77% of patients stayed in the same cluster), followed by the severe cluster (51%), and moderate cluster had the lowest stability (3%). A minority of patients from mild cluster moved to severe cluster (19%). In severe cluster, a larger number moved to moderate cluster (40%) and fewer to mild cluster (9%). CONCLUSION: Three distinct clusters of symptom intensity were documented in patients with SLE in association with cognitive function. There was a lower tendency for patients in the mild and severe clusters to move but not moderate cluster over the course of a year. This may demonstrate an opportunity for intervention to have moderate cluster patients move to mild cluster instead of moving to severe cluster. Further studies are necessary to assess factors that affect movement into moderate cluster.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Assessing Patient Values and Preferences to Inform the 2023 American College of Rheumatology/American College of Chest Physicians Interstitial Lung Disease Guidelines.

OBJECTIVE: Patient engagement is critical to clinical practice guideline (CPG) development. This work presents our approach to ascertaining patients' values and preferences to inform the American College of Rheumatology guidelines for screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We conducted a cross-sectional qualitative study of a purposefully sampled Patient Panel using a modified content analytic approach. The study team reviewed text transcripts from the Patient Panel discussion to identify themes and develop a clustered thematic schema. RESULTS: Twenty-one patients (75% women) participated, with a mean age of 53 years (range 33-73). Patients had one or more SARDs: systemic sclerosis (38%), Sjögren disease (38%), idiopathic inflammatory myopathy (33%), rheumatoid arthritis (24%), and mixed connective tissue disease (10%). We identified 10 themes in 4 thematic clusters: communication, screening and monitoring, treatment goals, and treatment adverse effects. Patients prioritized recognizing ILD symptoms, importance of ILD screening and close monitoring, goals of survival and improving quality of life, and willingness to accept treatment risks provided that there is close communication with providers. Patient representatives shared patients' priorities and insight at the Voting Panel meeting, influencing multiple guideline recommendations. CONCLUSION: Patient engagement fosters a holistic approach to CPG development, leading to recommendations aiming for the best clinical outcomes while prioritizing outcomes important for patients. The patient-identified themes played a critical role in ILD guideline development and provide core elements for shared decision-making as clinicians make management and therapeutic decisions with patients with SARD-associated ILD.

Effects of Radiotherapy for Malignancy in Systemic Sclerosis: A Systematic Review.

OBJECTIVE: Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We conducted a systematic review to evaluate the effects of radiotherapy on SSc outcomes and radiotherapy-related toxicity. METHODS: MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched for SSc and radiotherapy. Inclusion criteria were SSc diagnosis, subsequent cancer development, and radiotherapy exposure. Outcomes were SSc manifestations (cutaneous thickening, pulmonary fibrosis, and SSc flare) and radiotherapy toxicity (acute and late) using Common Terminology Criteria for Adverse Events for grading. Grade 1 and 2 toxicities were categorized as nonsevere and grade 3 to 5 toxicities as severe. RESULTS: Of 121 patients with SSc undergoing radiotherapy (mean age 56.4 years, 83.3% female, median radiotherapy dose 50 Gy), most did not show worsened SSc skin thickening (74.5%) or pulmonary complications (74%) post radiotherapy. In retrospective studies, the average rates of acute adverse effects were 57.3% for nonsevere and 25.8% for severe, whereas the rates of late adverse effects were 32.4% for nonsevere and 24% for severe. CONCLUSION: Although most patients with SSc do not exhibit significant worsening of SSc manifestations post radiotherapy, there is a variable risk of acute and late toxicity. These findings suggest that although radiotherapy may be a viable option for patients with cancer with SSc, it requires caution.

Sex-Related Differences in Dispensation of Rheumatic Medications in Older Patients With Inflammatory Arthritis: A Population-Based Study.

OBJECTIVE: The aim of our study was to compare dispensation of rheumatic medications between older male and female patients with early rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: This retrospective cohort study was performed using health administrative data from Ontario, Canada (years 2010-2017), on patients with incident RA and PsA, who were aged ≥ 66 years at the time of diagnosis. Yearly dispensation of rheumatic drugs was compared between older male and female patients for 3 years after diagnosis using multivariable regression models, after adjusting for confounders. The groups of drugs included in the analysis were disease-modifying antirheumatic drugs (DMARDs) classified as conventional synthetic DMARDs (csDMARDs) and advanced therapy (biologic DMARDs and targeted synthetic DMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and oral corticosteroids. Results were reported as odds ratios (ORs) with 95% CIs. RESULTS: We analyzed 13,613 patients (64% female) with RA and 1116 patients (57% female) with PsA. Female patients with RA were more likely to receive opioids (OR 1.39, 95% CI 1.22-1.58 to OR 1.51, 95% CI 1.32-1.72) and NSAIDs (OR 1.14, 95% CI 1.04-1.25 to OR 1.16, 95% CI 1.04-1.30). Dispensation of DMARDs showed no sex difference in either group. Subgroup analyses showed more intense use of advanced therapy in the RA cohort and of csDMARDs in the PsA cohort when patient and physician sex was concordant. CONCLUSION: This study did not identify any sex difference in the use of DMARDs among older patients with RA and PsA. The reasons for the higher use of opioids and NSAIDs among female patients with RA warrant further research.

Defining the key clinician skills and attributes for competency in managing patients with osteoporosis and fragility fractures.

Osteoporosis and fragility fractures are managed by clinicians across many medical specialties. The key competencies of clinicians delivering bone health care have not been systematically established. We aimed to develop a decision rule to define the threshold of adequate skills and attributes associated with clinical competency in bone health for a clinician serving as a referral source for bone health care. Using a modified-Delphi method, we invited clinicians with expertise in treating osteoporosis and representatives of patient advocacy groups focused on bone health to create a list of desirable characteristics of a clinician with bone health competency. Characteristics were defined as "attributes" with "levels" within each attribute. Participants prioritized levels by perceived importance. To identify the cut points for defining adequate competency, participants next ranked 20 hypothetical clinicians defined by various levels of attributes from highest to lowest likelihood of having adequate bone health competency. Lastly, we conducted a discrete choice experiment (DCE) to generate a weighted score for each attribute/level. The threshold for competency was a priori determined as the total weighted score at which ≥70% of participants agreed a clinician had adequate bone health competency. Thirteen participants generated lists of desirable characteristics, and 30 participants ranked hypothetical scenarios and participated in the DCE. The modified-Delphi exercise generated 108 characteristics, which were reduced to 8 categories with 20 levels with associated points. The maximum possible score was 25 points. A summed threshold score of >12 points classified a clinician as having adequate bone health competency. We developed a numeric additive decision rule to define clinicians across multiple specialties as having adequate competency in managing bone health/osteoporosis. Our data provide a rigorously defined criteria for a clinician with competency in bone health and can be used to quantitate the skills of clinicians participating in bone health research and clinical care.

Osteoporosis and fragility fractures are managed by clinicians across many medical specialties. The key skills of clinicians delivering bone health care have not been systematically established. We invited clinicians with expertise in treating osteoporosis and representatives of patient advocacy groups focused on bone health to create a list of desirable characteristics of a clinician with bone health competency. Participants next ranked 20 hypothetical clinicians defined by various characteristics from highest to lowest likelihood of having adequate bone health competency. Lastly, we generated a weighted score for each characteristic. The threshold for competency was determined as the total weighted score at which ≥70% of participants agreed a clinician had adequate bone health competency. The maximum possible score was 25 points, and a summed threshold score of >12 points classified a clinician as having adequate bone health competency. Our data provide a rigorously defined criteria for a clinician with competency in bone health and can be used to quantitate the skills of clinicians participating in bone health research and clinical care.

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.

Understanding the Employment Landscape in People With Systemic Sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) can restrict employment participation. Our objectives were to comparatively evaluate health factors, work factors, and workplace accommodations between those who are employed and those who recently gave up employment. METHODS: A cross-sectional study was conducted of employed and recently working, but now unemployed, individuals with SSc. Demographics, employment sectors, health factors, flare frequency, work context, and information about the need, availability, and use of workplace supports were collected. RESULTS: Participants were 140 individuals (108 [77.1%] women, 32 [22.9%] men), of whom 110 (78.6%) were employed and 30 (21.4%) were unemployed. Participants worked in education/health/sciences/arts (n = 51, 36.4%), sales/retail (n = 23, 16.5%), banking/insurance/business/technology (n = 22, 15.7%), government (n = 15, 10.7%), construction/utilities (n = 10, 7.1%), and manufacturing/agriculture/mining/logging (n = 10, 7.1%). Employed participants had a lower mean age (48.4 vs 54.3 yrs), and higher level of education (77.3% with postsecondary education vs 22.7% without). Those who had no flares were more frequently employed (41.7%), compared to those who had 1 to 2 flares (35.2%) and ≥ 3 flares (23.1%). The availability of workplace accommodations differed significantly between the employed and unemployed: flexible hours (74.5% vs 40%, P = 0.0005), more rest periods (73.6% vs 46.7%, P = 0.0001), special equipment (82.7% vs 46.7%, P < 0.0001), and work schedule flexibility (66.4% vs 33.3%, P = 0.003). CONCLUSION: Health factors alone do not differentiate those who are employed and those who gave up employment. This study lays the groundwork for where SSc-specific efforts in workplace policies and practices should be directed, especially workplace support.

OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set.

BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

Gender differences in juvenile systemic sclerosis patients: Results from the international juvenile scleroderma inception cohort.

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

Approach to Systemic Sclerosis Patient Assessment: How Does Patient Subsetting Help?

Systemic sclerosis (SSc) is a heterogeneous disease comprising of a wide spectrum of ages of onset, sex-based differences, ethnic variations, disease manifestations, differential serologic profiles, and variable response to therapy resulting in reduced health-related quality of life, disability, and survival. The ability to subset groups of patients with SSc can assist with refining the diagnosis, guide appropriate monitoring, inform aggressiveness of immunosuppression, and predict prognosis. The ability to subset patients with SSc has several important practical implications for patient care.

Advanced Autoantibody Testing in Systemic Sclerosis.

Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. Many clinicians now have improved access to an expanded profile of autoantibody testing. In this narrative review article, we review the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in people with systemic sclerosis.

Quality Measures in Systemic Sclerosis.

Quality improvement is an emerging field, that applies principles of improvement science and utilizes measurement methods with the aim of improving patient care. Systemic sclerosis (SSc) is a systemic autoimmune rheumatic disease associated with increased healthcare burden, cost, morbidity, and mortality. Gaps in delivering care to patients with SSc have been consistently observed. In this article, we introduce the discipline of quality improvement and its use of quality measures. We summarize and comparatively evaluate three sets of quality measures that have been proposed to evaluate the quality of care of patients with SSc. Finally, we highlight the areas of unmet needs and indicate future directions for quality improvement and quality measures in SSc.

State-of-the-art evidence in the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.

Epidemiology and Survival of Systemic Sclerosis-Sarcoidosis Overlap Syndrome.

OBJECTIVE: We evaluated the epidemiology, manifestations, serology, comorbidities, and survival among patients with systemic sclerosis (SSc) with and without sarcoidosis. METHODS: We conducted a retrospective cohort study comparing patients with SSc with and without sarcoidosis. All patients fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc. Sarcoidosis was based on physician diagnosis and/or confirmatory biopsy. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier curves. RESULTS: We included 1977 patients (1971 with SSc, 6 with SSc-sarcoidosis) with a SSc-sarcoidosis prevalence of 0.30%. Sarcoidosis frequently preceded SSc (66.66%). The most frequent sarcoidosis manifestations were pulmonary (66.66%), lymphadenopathy (66.66%), arthritis (50%), cutaneous (33.33%), and hepatic (16.66%). Patients with SSc and SSc-sarcoidosis had female to male sex ratios of 4.5:1 vs 5:1 and median ages of SSc onset of 48.3 vs 43.8 years, respectively. Interstitial lung disease (35% vs 66.66%) and pulmonary hypertension (24.91% vs 50%) tended to occur more frequently whereas abnormal nailfold capillaries (34.7% vs 16.66%) and digital ulcers (33.33% vs 16.66%) tended to occur less frequently among patients with SSc-sarcoidosis, but the differences were not significant. There was an increased frequency of stroke among the patients with SSc-sarcoidosis (relative risk 8.59, 95% CI 1.02-72.00). The median survival times were 23.4 years for SSc-sarcoidosis and 18.6 years for SSc, with no differences in survival curves (log-rank test, P = 0.55). CONCLUSION: Sarcoidosis in SSc is rare but appears to occur more frequently than in the general population. It is associated with pulmonary, lymph node, cutaneous, joint, and hepatic involvement. Stroke occurs more frequently in patients with SSc-sarcoidosis but with no differences in survival.

Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis.

BACKGROUND: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression. METHODS: A total of 280 subjects were studied, including 50 ANA- healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. RESULTS: Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. CONCLUSION: Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression.