Diagnosis Of Systemic Sclerosis Research Articles

Within-person fluctuations of fatigue in patients with a clinical diagnosis of systemic sclerosis and its relationship with mood, pain, sleep and physical activity

Objectives: To explore the within-person fluctuations of fatigue in systemic sclerosis and its association with negative affect, positive affect, pain, perceived exertion of physical activity and quality of sleep. Methods: We performed an ecological momentary assessment study in adult patients with a clinical diagnosis of systemic sclerosis. During 14 days, patients completed daily assessments of fatigue severity, negative affect, positive affect, pain, quality of sleep and perceived exertion of physical activity at four fixed time points. The day-to-day fluctuations in fatigue were quantified by the intra-individual variance and probability of acute change, capturing the magnitude and frequency of clinical relevant within-person day-to-day fluctuations, respectively. Using multilevel models, the within-person association between fatigue and the daily assessments were analysed. Results: Fifty-seven patients with systemic sclerosis participated. The mean (standard deviation) intra-individual variance was 1.08 (0.42) and the probability of acute change was mean (standard deviation) 0.40 (0.14), ranging from 0.08 to 0.77. For fatigue, a within-person variation of 51% was observed. Multilevel analyses showed that higher average levels and daily increases in negative affect, pain and perceived exertion of physical activity were associated with more fatigue, while the opposite was observed for positive affect and quality of sleep. Positive affect demonstrated the strongest association with fatigue fluctuations. Conclusion: This is the first quantitative study showing that fatigue in systemic sclerosis is characterized by a dynamic course and that approximately half of the day-to-day fluctuations within persons are clinically meaningful. Furthermore, our results indicate that integrating activities with positive impact on mood into fatigue treatment strategies might reduce the frequency of fatigue fluctuations.

E062 Nailfold capillaroscopy: its application in routine clinical practice

Abstract Background/Aims Nailfold capillaroscopy (NFC) is a non-invasive tool to evaluate the structural microvascular abnormalities found in systemic sclerosis (SSc). NFC allows for the visualization of the capillary bed at the nailfold, providing valuable insights into the structure and function of these capillaries. NFC helps differentiate primary from secondary Raynaud’s phenomenon (RP). Abnormal NFC is included in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and due to its predictive value of developing SSc is included in the Very Early Diagnosis of SSc (VEDOSS) criteria. Dudley Group NHS FT runs a consultant-led service supported by a specialty trainee where clinical review is carried out alongside NFC using video capillaroscopy. Patients can be referred to this clinic from rheumatology or respiratory colleagues. Methods We audited all patients who had attended a monthly NFC clinic between September 2021 and October 2023. We reviewed clinical letters and electronic patient record system and collected details of: demographics; immunology; clinical characteristics; reason for attending the clinic; NFC findings; and diagnosis. NFC findings were classified as normal or abnormal (to include scleroderma pattern and non-specific changes). Data was analysed using excel for individual variables and their comparison with nailfold capillaroscopy results. Results We identified 80 patients, of which 63 (79%) were females and median age was 54.5 years. ANA was positive in 64 (80%) patients, SSc and myositis immunology blots were positive in 41 (51%) and 4 (5%) respectively. Clinical characteristics included RP in 71 (89%) and interstitial lung disease (ILD) in 17 (21%). The reasons for attending the NFC clinic were categorised as: to exclude secondary causes of RP (52; 65%); to aid diagnosis of suspected SSc (23; 29%); surveillance of known SSc (5; 6%). NFC was normal in 42 patients. In the 38 patients where NFC was abnormal the clinical diagnosis was categorised as: primary RP (8; 10%); SSc spectrum of disease (17; 21%); and another CTD (20; 25%). Of patients with SSc spectrum of disease: 24% (4/17) had a diagnosis of VEDoSS; 47% (8/17) Limited Cutaneous SSc; and 29% (5/17) Diffuse SSc. The presence of RP and ANA was not significantly different in patients with abnormal NFC. There was a non-significant association between the presence of ILD and abnormal NFC. 9/17 (52%) patients with ILD had an abnormal NFC compared to 18/63 (29%) patients without ILD (p = 0.059). Conclusion NFC is a simple procedure in conjunction with a clinical review to enhance the early diagnosis of SSc and exclusion of secondary Raynaud’s. It supports education and training as a tool for learning as being part of the curriculum. Disclosure S.A. Tabassum: None. K.M.J. Douglas: None. E. Udeshika: None.

Erasmus syndrome: A rare case report

Erasmus syndrome is a rare clinical entity in which systemic sclerosis develops following exposure to silica with or without development of silicosis. There are very few cases reported in literature from India. Here we report a case of Erasmus syndrome in a 52 years male who is a stone crusher by occupation for last 22 years presented with dry cough, low grade irregular fever, progressive shortness of breath, slowly progressive sclerodactyly and features suggestive of Raynaud’s phenomenon. Radiological evaluations revealed multiple subpleural and centrilobular nodules in bilateral upper, lower lobes and right middle lobe, conglomerated nodular opacities (progressive massive fibrosis- PMF). There was pleural thickening and calcification, bronchial dilatation and fibrosis, calcified right hilar and mediastinal lymphadenopathy. Serological markers like Anti Scl-70 antibody came out to be positive (3+) Based on clinical features diagnosis of systemic sclerosis was made. Based on exposure history and radiology silicosis was diagnosed. Association of silicosis and systemic sclerosis establishes the diagnosis of Erasmus syndrome. Treatment was started with Prednisone, cyclophosphamide and Nifedipine. Strict avoidance to cold and regular follow-up was advised.

Identification and validation of autophagy-related genes in SSc.

Multiple organs are affected by the complex autoimmune illness known as systemic sclerosis (SSc), which has a high fatality rate. Genes linked to autophagy have been linked to the aetiology of SSc. It is yet unknown, though, whether autophagy-related genes play a role in the aetiology of SSc. After using bioinformatics techniques to examine two databases (the GSE76885 and GSE95065 datasets) and autophagy-related genes, we were able to identify 12 autophagy-related differentially expressed genes that are linked to the pathophysiology of SSc. Additional examination of the receiver operating characteristic curve revealed that SFRP4 (AUC = 0.944, P < 0.001) and CD93 (AUC = 0.904, P < 0.001) might be utilized as trustworthy biomarkers for the diagnosis of SSc. The SSc group's considerably greater CD93 and SFRP4 expression levels compared to the control group were further confirmed by qRT-PCR results. The autophagy-related genes SFRP4 and CD93 were found to be viable diagnostic indicators in this investigation. Our research sheds light on the processes by which genes linked to autophagy affect the pathophysiology of SSc.

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies

IntroductionTh/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. MethodsILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. ResultsFifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. ConclusionsOnly a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies.

Allostatic overload in the medically ill patients: Results from an observational study

The present study aimed at evaluating the prevalence of allostatic overload (AO) among subjects with different medical diseases and explore whether medically ill patients with or without AO differ for specific clinical features (i.e., co-occurring mental or psychosomatic disorders). An observational cross-sectional study was carried out. Outpatients with a diagnosis of blood cancer, systemic sclerosis, or migraine received a clinical assessment which included the Mini International Neuropsychiatric Interview or the Structured Clinical Interview for DSM-5 and the Diagnostic Criteria for Psychosomatic Research-Revised Semi-Structured Interview (DCPR-R SSI). Four hundred and thirty-nine outpatients were enrolled. Among them, 39 (8.9%) had a diagnosis of blood cancer, 200 (45.5%) had a diagnosis of systemic sclerosis, and 200 (45.5%) had a diagnosis of migraine. A total of 104 (23.7%) patients had a DCPR-R diagnosis of AO. Patients with a diagnosis of blood cancer, migraine, or systemic sclerosis did not differ for DCPR-R AO prevalence (P = 0.082). Based on multiple regression analysis, medically ill patients with DCPR-R AO were more likely to satisfy the diagnosis of DCPR-R illness denial (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.04 &amp;ndash; 8.58), conversion symptoms (OR = 5.32, 95% CI = 1.16 &amp;ndash; 24.38), or demoralization (OR = 2.57, 95% CI = 1.08 &amp;ndash; 6.11) and a DSM-5 diagnosis of major depressive episode/disorder (OR = 1.90, 95% CI = 1.03 &amp;ndash; 3.50), if compared to those without DCPR-R AO. DCPR-R AO is a clinically useful transdiagnostic feature potentially associated with other psychosomatic syndromes and mental disorders that may contribute to the disease burden and the poor global health conditions of medically ill patients.

High mobility box protein-1 may be a new biomarker in active interstitial lung disease of systemic sclerosis

&lt;b&gt;Introduction:&lt;/b&gt; To investigate the significance of high mobility group box 1 (HMGB1) levels as both an immune and inflammatory mediator in systemic sclerosis (SSC) patients with interstitial lung disease (SSC-ILD) and whether HMGB1 levels could be a biomarker for progression and disease activity.&lt;br /&gt; &lt;b&gt;Materials &amp;amp; methods:&lt;/b&gt; Our study included 27 patients diagnosed with SSC according to the 2013 ACR/EULAR classification criteria, along with 12 healthy controls (HC). Among the patients with a diagnosis of SSC, they were further categorized into two groups based on the presence of ILD with 19 patients having lung involvement and eight patients without. In ILD-positive group, the activity of the involvement was assessed using the simple Goh algorithm. Serum levels of HMGB1 were evaluated in all groups using ELISA method.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Significantly higher serum HMGB1 levels were found in patients with SSC-ILD active disease when compared to those with inactive ILD involvement and HC (14.01 mg/dl vs. 7.87 mg/dl and 8.04 mg/dl).&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Serum HMGB1 levels reflect the disease activity in SSC-ILD. HMGB1 could be used for a potential biomarker for detecting active lung disease.

Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.

We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4709724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P=0.01), younger (mean age of 67.4 vs. 71.4; P<0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P<0.01), hyperlipidaemia (39.1% vs. 52.9%; P<0.01), diabetes (22.5% vs. 49.1%; P<0.01), obesity (13.2% vs. 25.0%; P<0.01), and hypertension (20.2% vs. 23.8%; P<0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P<0.01) and pulmonary hypertension (36.6% vs. 12.7%; P<0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P<0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P<0.01), Black (15.7% vs. 13.0%; P<0.01), and Hispanic (13.3% vs. 6.9%; P<0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P<0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P=0.02) and higher hospitalization costs ($67363 vs. $57128; AMD: 198.9; 95% CI: -4780 to 5178; P=0.93). In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors.

Predictors of reduced quality of life in patients with systemic sclerosis

Predictors of reduced quality of life in patients with systemic sclerosis

[Systemic sclerosis].

Systemic sclerosis (SSc) is avery heterogeneous, chronic, rare, but socioeconomically important disease with asevere disease course and severe impairment of the quality of life of affected patients. Overview of the current state of research on the pathogenesis, diagnosis and therapy of SSc. A literature search was performed. The pathogenesis of SSc is not fully understood. ACR/EULAR criteria allow the diagnosis of early forms of SSc. Classification into limited cutaneous SSc and diffuse cutaneous SSc is of prognostic and therapeutic relevance. New organ-specific treatment options for SSc have led to improved quality of life and prognosis.

Periostin expression in uninvolved skin as a potential biomarker for rapid cutaneous progression in systemic sclerosis patients: a preliminary explorative study.

This study aimed to evaluate periostin serum levels and skin expression in patients with systemic sclerosis (SSc). We enrolled 35 patients with diffuse (d-SSc) or limited (l-SSc) SSc, 15 patients with very early diagnosis of systemic sclerosis (VEDOSS), and 30 sex-matched healthy controls. Periostin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). Periostin skin expression was determined by immunohistochemistry (IHC) on paired involved and uninvolved 5-mm skin biopsy samples in a subgroup of 10 d-SSc and 10 L-SSc patients. A 12-month follow-up was considered. We included 50 patients (mean age 53.1 ± 16.1 years; women 94%; mean disease duration 38.2 ± 45.1 months; anti-centromere 50%; anti-Scl70 40%), 35 of them with a definite SSc (68.8% l-SSc; 31.4% d-SSc; mean mRSS 9.0 ± 7.2) and 15 with VEDOSS; 30 controls were also included in this study. Periostin serum levels were higher in SSc patients compared to controls (32.7 ± 8.0 ng/mL vs. 27.7 ± 7.3 ng/mL; p < 0.001), while these levels were comparable among different groups of patients (29.7 ± 6.9 ng/mL in VEDOSS, 33.4 ± 7.8 ng/mL in lc-SSc; and 34.0 ± 8.5 in dc-SSc; p = ns). SSc patients with digital ulcers had higher periostin serum levels (36.2 ± 7.9 ng/mL vs. 30.6 ± 7.3 ng/mL, p < 0.02). Samples from the involved skin of l-SSc and d-SSc patients showed a significant dermal expression of periostin; an identical periostin expression was evident in the uninvolved skin of patients with d-SSc. In 7 out of 10 L-SSc patients, periostin expression was absent on uninvolved skin. In the remaining three l-SSc patients, a mild periostin expression on IHC was detectable on uninvolved skin and all of these three l-SSc patients presented a dramatic skin progression. Periostin skin expression may be a useful biomarker to indicate the presence of a disease at a higher risk of rapid cutaneous involvement.

History of pre-eclampsia does not appear to be a risk factor for vascular phenotype in women with systemic sclerosis

BackgroundVascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection.ObjectivesTo explore risk factors for a vascular phenotype...

Development and validation of a new diagnostic prediction model of ENHO and NOX4 for early diagnosis of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis. The challenge of early diagnosis, along with the lack of effective treatments for fibrosis, contribute to poor therapeutic outcomes and high mortality of SSc. Therefore, there is an urgent need to identify suitable biomarkers for early diagnosis of SSc. Three skin gene expression datasets of SSc patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) database (GSE130955, GSE58095, and GSE181549). GSE130955 (48 early diffuse cutaneous SSc and 33 controls) were utilized to screen differentially expressed genes (DEGs) between SSc and normal skin samples. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) were performed to identify diagnostic genes and construct a diagnostic prediction model. The results were further validated in GSE58095 (61 SSc and 36 controls) and GSE181549 (113 SSc and 44 controls) datasets. Receiver operating characteristic (ROC) curves were applied for assessing the level of diagnostic ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to verify the diagnostic genes in skin tissues of out cohort (10 SSc and 5 controls). Immune infiltration analysis were performed using CIBERSORT algorithm. A total of 200 DEGs were identified between SSc and normal skin samples. Functional enrichment analysis revealed that these DEGs may be involved in the pathogenesis of SSc, such as extracellular matrix remodeling, cell-cell interactions, and metabolism. Subsequently, two critical genes (ENHO and NOX4) were identified by LASSO and SVM-RFE. ENHO was found down-regulated while NOX4 was up-regulated in skin of SSc patients and their expression levels were validated by above three datasets and our cohort. Notably, these differential expressions were more pronounced in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc. Next, we developed a novel diagnostic model for SSc using ENHO and NOX4, which demonstrated strong predictive power in above three cohorts and in our own cohort. Furthermore, immune infiltration analysis revealed dysregulated levels of various immune cell subtypes within early SSc skin specimens, and a negative correlation was observed between the levels of ENHO and Macrophages M1 and M2, while a positive correlation was observed between the levels of NOX4 and Macrophages M1 and M2. This study identified ENHO and NOX4 as novel biomarkers that can be serve as a diagnostic prediction model for early detection of SSc and play a potential role in the pathogenesis of the disease.

Retracted: The Function of Retinal Thickness and Microvascular Alterations in the Diagnosis of Systemic Sclerosis.

[This retracts the article DOI: 10.1155/2023/1805938.].

Outcomes in systemic sclerosis patients hospitalized with COVID-19: Insight from the National Inpatient Sample

Objective: COVID-19, a respiratory infection caused by the novel coronavirus SARS-CoV-2, can cause varying degrees of illness ranging from mild respiratory illness to severe respiratory failure. Systemic sclerosis is a chronic autoimmune disease, with an increased prevalence of infections as compared to the general population. In this study, we compare the clinical outcomes and resource utilization for COVID-19 hospitalizations in patients with and without systemic sclerosis. Methods: We used the National Inpatient Sample database, 2020, to study the characteristics, morbidity, mortality, cost, and resource utilization among primary COVID-19 hospitalizations with and without systemic sclerosis. Results: There were 1,050,040 patients aged ⩾ 18 years with a diagnosis of COVID-19. Of these, 775 (0.07%) patients had a secondary diagnosis of systemic sclerosis. Although there was no statistically significant difference regarding individual outcomes; in-hospital mortality, vasopressor use, cardiac arrest, acute kidney injury, and disposition to facility were numerically higher in hospitalizations with systemic sclerosis. The composite endpoint of major adverse events was higher in the systemic sclerosis cohort (adjusted odds ratio 1.52, 95% confidence interval: 1.06–2.17, p = 0.022). Conclusion: COVID-19 patients with systemic sclerosis had worse outcomes (i.e. higher composite endpoint of major adverse events) than those without systemic sclerosis. Further studies are needed to establish a better understanding of the relationship between COVID-19 and systemic sclerosis.

Abstract 14871: Mitral Valve Involvement in Systemic Sclerosis, Post COVID-19 Infection

Introduction: We report a case of mitral valve regurgitation as cardiac involvement of systemic sclerosis (SSc) in a 52-year-old woman post COVID-19 infection. Case Description: 52-year-old female presented with new-onset, progressive dyspnea, dryness and thickness of the skin, intermittent palpitations, and weight loss 3 months after recovered from COVID-19. Initial laboratory studies showed low hemoglobin levels and elevated pro-BNP, troponin-T, hs-CRP and ESR. An autoimmune panel was ordered and revealed positive antinuclear antibodies (ANA) and positive scleroderma related antibodies (anti-RNA polymerase III). Chest radiography and Chest CT without contrast both showed septal and bronchial wall thickening. A transthoracic echocardiogram was performed and showed a severely dilated left atrium and mildly thickened mitral valve leaflets with severe mitral regurgitation. A transesophageal echocardiogram revealed a thickened anterior mitral leaflet and restricted mobility of the posterior leaflet with mitral regurgitation being moderate in severity. These findings were consistent with the reported changes seen on echocardiogram and in autopsies in patients with SSc. The diagnosis of SSc in this patient was made and the patient was started on mycophenolate. Conclusions: This case highlights the possible mechanisms through which COVID-19 may trigger the development of autoimmune and inflammatory reactions which, in our case, lead to the development of mitral regurgitation as a sequela of SSc. Imagine 1. Imagine 2.

Respiratory failure in systemic sclerosis.

Systemic sclerosis (SSc) can lead to dyspnea and respiratory failure through multiple mechanisms, making a precise diagnosis particularly challenging, especially amid the current COVID-19 pandemic. In this report, we present a case involving a 26-year-old female who had previously undiagnosed SSc. She experienced acute respiratory failure necessitating orotracheal intubation. Following an extensive evaluation, the patient exhibited skin thickening, kidney failure, thrombocytopenia, microangiopathic anemia, and an antinuclear antibody with a nuclear fine speckled pattern at a titer of 1:320. A diagnosis of SSc complicated by scleroderma renal crisis (SRC) was established. The patient's condition improved after undergoing hemodialysis, receiving an angiotensin-converting enzyme inhibitor, and undergoing cyclophosphamide treatment. Subsequently, she demonstrated sustained improvement during a follow-up period of 20months.

Economic and Health Care Resource Use Burden of Systemic Sclerosis.

To describe the health care resource use (HCRU) and costs of patients with systemic sclerosis (SSc) prior to and after diagnosis. This retrospective study used a claims data set (Merative MarketScan; 2015-2019). Eligible patients with SSc were identified by diagnosis codes and required at least 24 months of enrollment without an SSc diagnosis before their first SSc claim and at least 12 months of enrollment thereafter. Total HCRU and costs were reported for three intervals: 2 years and 1 year before and 1 year after index diagnosis. A general population cohort without SSc was matched 1:1 to the SSC cohort on age and sex for comparison. Eligibility criteria identified 902 patients with SSc (mean age: 54 years old; 85% female). Mean per-member per year costs increased each year from $22,383 to $29,708 to $47,095, 2 years before, 1 year before, and 1 year after index diagnosis versus $10,232 to $9656 to $9714 in the general population cohort. Outpatient settings represented the largest proportion of cost 1 year after SSc diagnosis ($16,392), followed by prescription drugs ($10,692), physician office ($10,523), and inpatient ($9448) settings. Patients with SSC accrued greater costs and required more services than a general population cohort. These elevated expenditures and HCRU were observed at least 2 years before an SSc diagnosis and increased over time, reflecting both the progressive, multisystem nature of SSc and potential challenges in diagnosis. These findings suggest that SSc poses a substantial burden on the US health care system and highlights the need for early diagnosis and effective therapies.

Esclerosis sistémica sine esclerodermia en una mujer con anticuerpos antinucleares centroméricos, afectación pulmonar y digestiva: Reporte de caso

Sine entities are rare in rheumatology. In progressive systemic sclerosis there is a variant of the limited cutaneous form called systemic sclerosis sine scleroderma, whose central feature is the lack of skin involvement, but visceral involvement is present. Positive anti-topoisomerase or anti-centromere antibodies confirm the diagnosis. We present the case of a 63-year-old woman with interstitial lung disease, intestinal transit involvement and Raynaud's phenomenon, with high titers of ANA with a centromeric pattern and positivity for anti-topoisomerase antibodies. When faced with a patient with Raynaud's phenomenon, visceral involvement and elevated ANA, specific antibodies should be requested for the diagnosis of systemic sclerosis in its sine variety.

Delayed adverse events following COVID-19 vaccination in patients with systemic sclerosis and other autoimmune diseases: a substudy of the COVAD-2 cohort.

Data on short-term safety of COVID-19 vaccination in patients with systemic sclerosis (SSc) were explored previously in the first COVID-19 vaccination in autoimmune diseases (COVAD) survey conducted in 2021. However, delayed adverse events (ADEs) (occurring > 7days post-vaccination) are poorly characterized in these patients with SSc. In this study, we analysed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HCs) using data from the second COVAD study conducted in 2022. The COVAD-2 study was a cross-sectional, patient self-reported global e-survey conducted from February to June 2022. Data on demographics, SSc/SAID disease characteristics, COVID-19 infection history, and vaccination details including delayed ADEs as defined by the Centre for Disease Control were captured and analysed. Among 17,612 respondents, 10,041 participants fully vaccinated against COVID-19 were included for analysis. Of these, 2.6% (n = 258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among patients with SSc, 18.9% reported minor, while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These frequencies were comparable to those of the ADEs reported by other patients with SAIDs and HCs. However, patients with SSc reported a higher frequency of difficulty in breathing than HCs [OR 2.3 (1.0-5.1), p = 0.042]. Patients with diffuse cutaneous SSc experienced minor ADEs [OR 2.1 (1.1-4.4), p = 0.036] and specifically fatigue more frequently [OR 3.9 (1.3-11.7), p = 0.015] than those with limited cutaneous SSc. Systemic sclerosis patients with concomitant myositis reported myalgia more frequently [OR 3.4 (1.1-10.7), p = 0.035], while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR 5.5 (1.5-20.2), p = 0.009] and dizziness [OR 5.9 (1.3-27.6), p = 0.024] than patients with SSc alone. A diagnosis of SSc did not confer a higher risk of delayed post-COVID-19 vaccine-related ADEs overall compared with other SAIDs and HCs. However, the diffuse cutaneous phenotype and coexisting autoimmune conditions including myositis and thyroid disease may increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post-COVID-19 vaccination period.