Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort.

OBJECTIVES: To untangle the association between smoking and systemic sclerosis (SSc). METHODS: In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA). RESULTS: Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for 'any organ progression' (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and 'any organ progression' (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and 'any organ progression' (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently. CONCLUSIONS: Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and 'any organ progression'.

Extrahepatic conditions of primary biliary cholangitis: A systematic review and meta-analysis of prevalence and risk.

BACKGROUND AND AIM: Many studies reported the prevalence of extrahepatic conditions (EHC) of primary biliary cholangitis (PBC), but the great heterogeneity existed across different studies. Therefore, we conducted the systematic review and meta-analyses to determine EHC prevalence and association with PBC. METHODS: We searched PUBMED and included observational, cross-sectional and case-controlled studies. A random or fixed effects model was used to estimate the pooled prevalence and odd ratio (OR) as appropriate. RESULTS: Of 5370 identified publications, 129 publications with 133 studies met the inclusion criteria. Sjögren's syndrome had the highest prevalence (21.4 % vs. 3 % in non-PBC individuals), followed by Raynaud's syndrome (12.3 % vs. 1 %), rheumatoid arthritis-like arthritis (5 % vs. 3 %), systemic sclerosis (3.7 % vs. 0 %) and systemic lupus erythematosus (2 % vs. 0 %). The prevalence of overall thyroid diseases (11.3 %), autoimmune thyroid diseases (9.9 %), osteoporosis (21.1 %), celiac disease (1 %) and chronic bronchitis (4.6 %) was also increased among PBC patients. CONCLUSION: This is the first exhaustive study on the old theme about EHC of PBC. Given increased prevalence of many EHCs in PBC patients, promptly recognizing these EHCs are of great importance for timely and precise diagnosis of PBC.

Neurodevelopmental profile in children born to mothers affected by systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease that can affect women of childbearing age. The long-term outcomes of their offspring remain poorly explored. Aim of this study was to detail the neurodevelopmental profile of children born to SSc mothers. METHODS: Twenty children (mean age: 96 ± 4.32 months; 10 males) born to SSc mothers were enrolled. We collected data on clinical history, neurological examination, cognitive profile and adaptive behavior in all subjects. According to the chronological age, we also investigated quality of life, behavioral characteristics, psychological functioning and self-image. RESULTS: All the children had normal neurological examination, cognitive profile and adaptive functioning, except for one (5 %) who suffered from Autism Spectrum Disorder. An important discrepancy was observed between parental and child opinion regarding the perception of quality of life, more compromised in the latter. We documented a risk for internalizing behavioral problems in 2 cases (10 %), for externalizing problems in 3 (15 %), for both in 1 (5 %) and for social and out-of-school activities in 5 (25 %). As regards psychological functioning, evaluated in 11 children, three (28 %) were at risk for anxiety, 1 (9 %) for depressive disorders and other 4 (36 %) for somatic disturbances. Emotional fragility and poor competence in metabolizing one's emotional experiences were observed in 9 out of the 13 subjects assessed (70 %). CONCLUSIONS: Children born to SSc women exhibit normal cognitive and adaptive abilities but an increased vulnerability to psychopathological problems and fragility in social functioning. These observations might reflect that children need to feel mature to accept maternal chronic disease that, in turn, may hinder support for offspring's social and emotional development.

Sarcopenia in systemic sclerosis: prevalence and impact-a systematic review and meta-analysis.

OBJECTIVE: This review aims to provide an estimate of sarcopenia prevalence and its impact on clinical characteristics in patients with systemic sclerosis (SSc). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, Web of Science and the Cochrane Central Register of Controlled Trials were systemically searched from inception to 24 May 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included observational studies that reported the prevalence of sarcopenia in patients with SSc. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed study selection and data extraction using standardised methods. Risk of bias was assessed using the Agency for Healthcare Research and Quality Scale and the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models. RESULTS: A total of 4583 articles were screened and 9 studies with data from 815 patients were included in the analysis (8 cross-sectional studies and 1 retrospective cohort study). The overall prevalence of sarcopenia in patients with SSc was 22% (95% CI 17% to 28%). Patients with SSc with sarcopenia had a poorer quality of life (mean difference -12.02; 95% CI -19.11 to -4.93) and higher C reactive protein (CRP) levels (standardised mean difference 0.67; 95% CI 0.35 to 1.00). CONCLUSIONS: Sarcopenia is common in patients with SSc. Patients with SSc with sarcopenia had a worse quality of life and higher CRP levels, based on our findings. Given the detrimental impact of sarcopenia on quality of life, future efforts aimed at early identification of sarcopenia in the clinical assessment of patients with SSc may have significance. PROSPERO REGISTRATION NUMBER: CRD42022368326.

Factors associated with satisfaction with social roles and activities among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network (SPIN) cohort cross-sectional study.

OBJECTIVE: The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities. METHODS: Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors. RESULTS: Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (-1.13, 95% CI -2.18 to -0.08); living in Canada (-1.33, 95% CI -2.40 to -0.26 (reference USA)) or the UK (-2.49, 95% CI -3.92 to -1.06); body mass index (-1.08 per SD, 95% CI -1.47 to -0.69); gastrointestinal involvement (-3.16, 95% CI -4.27 to -2.05); digital ulcers (-1.90, 95% CI -3.05 to -0.76); moderate (-1.62, 95% CI -2.78 to -0.45) or severe (-2.26, 95% CI -3.99 to -0.52) small joint contractures; interstitial lung disease (-1.11, 95% CI -1.97 to -0.25); pulmonary arterial hypertension (-2.69, 95% CI -4.08 to -1.30); rheumatoid arthritis (-2.51, 95% CI -4.28 to -0.73); and Sjogren's syndrome (-2.42, 95% CI -3.96 to -0.88). CONCLUSION: Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

Association between systemic sclerosis and risk of cerebrovascular and cardiovascular disease: a meta-analysis.

We aimed to evaluate the association between systemic sclerosis (SSc) and major cerebrovascular/cardiovascular risks through a systematic approach. Databases were systematically searched from their inception to October 10, 2023 for studies comparing cerebrovascular/cardiovascular event rates between patients with SSc and controls. The primary outcome was the stroke risk in patients with SSc. Secondary outcomes included risk of myocardial infarction (MI), cardiovascular disease (CVD), peripheral vascular disease (PVD), and venous thromboembolism (VTE). Seventeen studies with 6,642,297 participants were included. SSc was associated with a significantly increased risk of stroke (HR, 1.64; 95% confidence interval [CI], 1.35-2.01), CVD (HR, 2.12; 95% CI, 1.36-3.3), MI (HR, 2.15; 95% CI, 1.23-3.77), VTE (HR, 2.75; 95% CI, 1.77-4.28), and PVD (HR, 5.23; 95% CI, 4.25-6.45). Subgroup analysis revealed a significantly increased stroke risk in the non-Asian group (HR, 1.55; 95% CI, 1.26-1.9), while the Asian group displayed a higher but not statistically significant risk (HR, 1.86; 95% CI, 0.97-3.55). The study found that SSc is associated with a significantly increased risk of cerebrovascular/cardiovascular events. These findings highlight the importance of vasculopathy in SSc and suggest the need for enhanced clinical monitoring and preventive measures in this high-risk population.

Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.

BACKGROUND: There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. METHODS: Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. RESULTS: Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83). CONCLUSIONS: Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.

OBJECTIVES: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort. METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719). FINDINGS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]). INTERPRETATION: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.

Longitudinal follow-up of mixed connective tissue disease and overlapping autoimmune diseases of childhood onset in the Afro-descendant population of the French West Indies.

INTRODUCTION: Overlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood. METHODS: Retrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa's criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM). RESULTS: Sixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4-17) with median follow up of 7.9 years (2.1-19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1-7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure. CONCLUSION: This is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.

Persistent Risk of Developing Autoimmune Diseases Associated With COVID-19: An Observational Study Using an Electronic Medical Record Database in Japan.

OBJECTIVE: This study aimed to investigate the risk of developing autoimmune diseases associated with coronavirus disease 2019 (COVID-19) in Japan, including long-term risks and risks specific to different variants of concern. METHODS: This observational study used an electronic medical record database in Japan. The COVID-19 group is composed of patients diagnosed with COVID-19, whereas the non-COVID-19 group had data sampled from the database. The outcomes of interest encompassed several autoimmune diseases, including rheumatoid arthritis, systemic sclerosis, and immunoglobulin G4-related disease, as well as a composite of these diseases (any autoimmune disease). We examined the relative risk of autoimmune diseases using standardized mortality ratio weighting and the Cox proportional hazards model. Subgroup analyses based on epidemic variants were performed. In addition, short- and long-term risks were investigated using piecewise constant hazard models. RESULTS: A total of 90,855 COVID-19 and 459,827 non-COVID-19 patients were included between January 16, 2020, and December 31, 2022. The relative risk of any autoimmune disease was 2.32 (95% confidence interval, 2.08-2.60). All the investigated outcomes showed a significant risk associated with COVID-19. Several autoimmune diseases exhibit a risk associated with COVID-19 in the short to long term, and the long-term risk is substantial for systemic sclerosis and immunoglobulin G4-related disease. The variant-specific risk varied across outcomes. CONCLUSIONS: COVID-19 is associated with an increased risk of developing autoimmune diseases in the Japanese population, and this effect persists for a long time. This study provides insights into the association between viral infections and autoimmunity.

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets.

BACKGROUND: Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as 'basket' endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials. The aim of this study is to describe prevalence, natural history and clinical factors associated with hand function deterioration in a longitudinal, multicentre, observational SSc cohort. METHODS: Hand function was captured through the validated Cochin Hand Function Scale in patients consecutively enrolled in a multicentre observational study and observed over 24 months. Minimal clinically important differences and patient acceptable symptom state were analysed as previously described. RESULTS: Three hundred and ninety-six consecutive patients were enrolled from 10 centres; 201 with complete follow-up data were included in the analysis. Median (IQR) disease duration was 5 (2-11) years. One hundred and five (52.2%) patients reported clinically significant worsening. Accordingly, the proportion of patients reporting unacceptable hand function increased over 2 years from 27.8% to 35.8% (p<0.001). Least absolute shrinkage and selection operator analysis identified male gender, disease subset, Raynaud's Condition Score, tenosynovitis and pain, as some of the key factors associated with worsening hand involvement. CONCLUSIONS: Hand function deteriorates over time in more than 50% of SSc patients despite available therapies. The analysis of factors associated with hand function worsening supports the involvement of both inflammation, vascular and fibrotic processes in hand involvement, making it a hallmark clinical manifestation of SSc. Our data are poised to inform the design of intervention studies to target this major driver of disability in SSc.

Systemic Sclerosis in Individuals With Exposure to World Trade Center Ground Zero Rescue and Recovery Efforts: A Case Series.

OBJECTIVE: The World Trade Center (WTC) attack in New York resulted in a dust plume containing silica, hydrocarbons, and asbestos. Autoimmune disorders have been reported among those with WTC site exposure. The characteristics of individuals developing systemic sclerosis (SSc) have not been previously described. The purpose of this study was to describe the features of patients with SSc with WTC exposure. METHODS: Data were collected from 11 patients with SSc or SSc spectrum conditions who reported exposure to the WTC site. Seven patients completed an exposure assessment. RESULTS: Of the 11 patients, the majority (n = 8) were female. The median (range) for age at diagnosis was 46 (36-75) years, time between exposure and first non-Raynaud phenomenon SSc symptom was 8 (1-19) years, and time between exposure and diagnosis was 11 (2-18) years. Fifty-five percent had SSc onset > 5 years from WTC exposure. Five patients had limited cutaneous SSc, 3 patients had diffuse cutaneous SSc, 1 patient with SSc features met criteria for mixed connective tissue disease (CTD), and 2 patients had undifferentiated CTD with features of SSc. Four patients had overlapping features with other CTDs. Interstitial lung disease (ILD) was present in 10 patients. Five of 11 patients had a history of tobacco use. Seven of 7 patients who completed the questionnaire reported other hazardous exposures outside of WTC. Of these, only 2 patients reported personal protective equipment use. CONCLUSION: A high frequency of ILD and overlap features were observed among patients with SSc with WTC exposure. Future studies are needed to characterize this association.

Prevalence and Characteristics of Patients With Systemic Sclerosis Fulfilling the 2019 EULAR/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

OBJECTIVE: There is limited literature describing the overlap of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and the studies have employed a range of case definitions. Our study used the new EULAR/American College of Rheumatology (ACR) SLE classification criteria to define SSc-SLE cases among our center's SSc cohort. METHODS: This is a single-center, retrospective study of a previously described cohort of patients with SSc. Patient data were re-abstracted to evaluate for fulfillment of the 2019 EULAR/ACR classification criteria for SLE. Demographic, laboratory, clinical features, and mortality were compared among patients with SSc-SLE and patients with SSc alone. RESULTS: Among the 402 patients with SSc that were analyzed, 40 (10%) fulfilled the 2019 EULAR/ACR SLE classification criteria. Neuropsychiatric and renal involvement were rare. An initial SLE diagnosis was purported in 43% of the patients with SSc-SLE and 7% of patients with SSc alone (P < 0.001). Patients with SSc-SLE were more likely to be female, African American, and with limited cutaneous SSc. Anti-U1-RNP antibody positivity prevalence was 30% among patients with SSc-SLE and 6.6% among patients with SSc alone (P < 0.001). Death during follow-up occurred in 12 patients (30%) with SSc-SLE and in 81 patients (22%) with SSc alone, but there was no difference in survival among the groups per log rank test (P = 0.404). CONCLUSION: Ten percent of patients with SSc fulfill the 2019 EULAR/ACR classification criteria for SLE. These patients comprise a distinct demographic, serologic, and clinical phenotype but have similar severe SSc-specific end-organ damage and mortality as patients with SSc alone. Patients with SLE with Raynaud phenomenon should be evaluated for SSc-specific autoantibodies and scleroderma organ involvement.

Impact of the COVID-19 Pandemic on Health Care Access and Diagnosis of Pulmonary Arterial Hypertension Among Patients With Systemic Sclerosis.

OBJECTIVE: Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH. METHODS: South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic. RESULTS: A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n = 109), Victorian respondents (n = 203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019. CONCLUSION: The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

Systemic sclerosis: changes in the incidence rates in the Finnish population during the years 1999-2018.

OBJECTIVE: The aim of our study was to examine changes in the incidence of systemic sclerosis (SSc) in Finland using two different classification criteria. METHOD: Medical records of patients who had been registered with ICD-10 code M34 from 1999 to 2018 in two university hospitals were reviewed retrospectively. This period was divided into 5 year periods: 1999-2003, 2004-2008, 2009-2013, and 2014-2018. Using American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria and clinical findings, we reclassified patients into four groups: diffuse SSc, limited SSc, sine SSc, or early SSc. In the same population, we also investigated whether the ACR 1980 criteria were fulfilled. RESULTS: In 1999-2018, 246 new patients with SSc and 45 patients with early SSc were identified using ACR/EULAR 2013 criteria. Of these patients, 70 fulfilled the ACR 1980 criteria. Using ACR/EULAR 2013 criteria, the increase in new diagnoses was statistically significant when comparing the fourth period with the first period (p = 0.0012). The increase was due to a rise in limited SSc. Mean annual incidence rates in these groups were 0.9, 1.2, 1.9, and 2.8 per 100 000 inhabitants ≥ 16 years old. An increasing trend was also seen when using ACR 1980 criteria, but this was not statistically significant. CONCLUSION: The incidence of SSc increased during the period between 1999-2003 and 2014-2018 using ACR/EULAR 2013, but not using ACR 1980 criteria. The increase was detected within a limited SSc subclass, owing to more sensitive classification criteria.

Standardized mortality ratios in systemic sclerosis: a meta-analysis assessing overall and sex- and disease subtype-specific differences.

OBJECTIVE: This study aims to evaluate the overall and sex- and illness subtype-specific standardized mortality ratios (SMRs) in patients with systemic sclerosis (SSc). METHODS: We searched and examined studies that compared the overall and sex- and illness subtype-specific SMRs in patients with SSc to those in the general population using MEDLINE, EMBASE, and Cochrane databases (until May 2023). We then conducted a meta-analysis of the overall and sex- and illness subtype-specific SMRs in patients with SSc. RESULTS: Overall, 29 studies including 30,673 patients with SSc and 5582 deaths met the inclusion criteria. Patients with SSc had a higher overall SMR than that in the general population (SMR: 2.742, 95% confidence interval [CI]: 2.224-3.38091, p < 0.001). The SMR significantly increased in populations from Europe, North America, Asia, and Oceania according to regional stratification. A sex-specific meta-analysis revealed a substantial increase in the SMR in both men and women (SMR: 3.598, 95% CI: 3.097-4.180, p < 0.001; SMR: 2.833, 95% CI: 2.4384-3.292, p < 0.001, respectively) and the mortality rate was higher in men compared to women. A substantial increase in the SMR in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) was observed in a disease subtype-specific meta-analysis. In addition, the SMR in the dcSSc group was higher than that in the lcSSc group (SMR: 4.726, 95% CI: 3.795-5.885, p < 0.001; SMR: 1.987, 95% CI: 1.586-2.489, p < 0.001, respectively). CONCLUSION: Our findings demonstrated that the mortality rate in patients with SSc was 2.74-times greater than that in the general population. The mortality rate was higher in men compared to women. Additionally, compared to patients with lcSSc, those with dcSSc showed much higher fatality rates.

The effect of calcium channel blockers on digital ulcers in systemic sclerosis: data from a prospective cohort study.

Digital ulcers (DU) are a common, severe vascular manifestation of systemic sclerosis (SSc) with few effective treatment options. Using data from the Australian Scleroderma Cohort Study (ASCS), we sought to evaluate the effect of calcium channel blockers (CCB) on the treatment and prevention of DU.Using data from 1953 participants, with a median of 4.34 years of follow-up, we used generalised estimating equations to evaluate the clinical characteristics associated with CCB use and ascertain the risk factors for the presence of DU at subsequent study visits. A time-dependent Cox-proportional hazard model was applied to evaluate the risk of future occurrence of DU with CCB use.Sixty-six percent of participants received CCB and patients with a history of DU were more likely to be prescribed a CCB (76.76% vs 53.70%, p < 0.01). CCB use was more frequent in patients with severe complications of DU including chronic DU (OR 1.47, p = 0.02), need for hospitalisation for iloprost (OR 1.30, p = 0.01) or antibiotics (OR 1.36, p = 0.04) and digital amputation (OR 1.48, p < 0.01). Use of CCB was more likely in patients who experienced DU at subsequent study visits (OR 1.32, p < 0.01) and was not associated with a decreased risk of the development of a first DU (HR 0.94, p = 0.65).CCB are frequently used in the management of SSc in the ASCS and their use is associated with severe peripheral vascular manifestations of SSc. However, our results suggest that CCB may not be effective in the healing or prevention of DU.