Search Results (22)

Marfan syndrome (MS), Loeys–Dietz syndrome (LDS), Beals–Hecht syndrome (BHS), Ehlers–Danlos syndrome (EDS), and individuals with undifferentiated connective tissue disease (UCTD) exhibit phenotypic overlap, suggesting a likelihood of genotypic coexistence. Our objective was to evaluate genetic variants (GVs), encoding 174 genes related to aortopathies, cardiomyopathies, arrhythmias, structural heart disease, and hypercholesterolemia, and their relationship to clinical and cardiovascular damage in these syndromes. This was a prospective study in Mexican patients with MS, LDS, EDS, BHS, and UCTD. One hundred and seventy-four genes related to hereditary diseases were studied using next-generation sequencing targeting coding regions. Of the 136 patients, 25 were identified with the recurrent and coexisting GV of MYBPC3. In the MS group, in addition to the presence of GV in FBN1, eight patients had GV in MYBPC3, six in FBN2, and five in COL3A1 and COL5A1. In the LDS group, in addition to GV in TGFBR1, TGFBR2, and SMAD3, four patients presented with GV in MYBPC3 and two with FBN2. In the BHS group, in addition to FBN2, two patients had GV in MYBPC3 and one with TGFBR2. In the UCTD group, nine patients had GV in MYBPC3 and two in COL5A1 and COL5A2. All syndromes coexisted with GV in genes related to arrhythmias, sarcomeres, and hypercholesterolemia. In EDS, coexistence with several sarcomere proteins was found. Full article

Non-viral myocarditis is rare but relatively more frequent in patients with systemic autoimmune diseases (such as systemic lupus erythematosus, SLE, and allied conditions) than in the general population. In rare cases, mRNA-based vaccines can also trigger non-viral myocarditis. Limited data are available about the cardiac safety of mRNA vaccines in this subset of patients. Here, we report data from a third-level hospital on long-term safety, leveraging on a previously described cohort of 13 consecutive patients with SLE, Undifferentiated (UCTD) and Mixed Connective Tissue disease (MCTD), and a history of myocarditis, who had received anti-COVID-19 vaccination between April 2021 and January 2022. Demographics and clinical data (including validated clinometric for SLE) were collected at baseline, at the first available visit following the primary vaccination cycle, after an additional 12 months, and at the last available follow-up after at least 36 months. Twelve patients, seven females, ten with SLE, one MCTD, and one UCTD, had a median follow-up of 41 (35–45) months. One patient was lost at follow-up. No disease flare or sign of myocarditis recurrence were observed. At last visit, all patients were in a low disease activity state (LLDAS), and all but one were in remission, according to the Definition of Remission in SLE (DORIS) criteria. No significant variations in disease activity or damage accrual nor in markers of inflammation and myocardial injury were observed. Our data suggest that mRNA-based anti-COVID-19 vaccines in patients with previous autoimmune myocarditis in the context of SLE and allied conditions have a good long-term safety profile. Full article

Background/Objectives: In clinical informatics, the term ‘information overload’ is increasingly used to describe the operational impediments of excessive documentation. While electronic health records (EHRs) are growing in abundance, many medical records (MRs) remain in legacy formats that impede efficient, systematic processing, contributing to the extenuating challenges of care fragmentation. Thus, there is a growing interest in using generative AI (genAI) for automated MR summarization and characterization. Methods: MRs for a set of 78 individuals were digitized. Some were known systemic lupus erythematosus (SLE) cases, while others were under evaluation for possible SLE classification. A two-pass genAI assessment strategy was implemented using the Claude 3.5 large language model (LLM) to mine MRs for information relevant to classifying SLE vs. undifferentiated connective tissue disorder (UCTD) vs. neither via the 22-criteria EULAR 2019 model. Results: Compared to clinical determination, the antinuclear antibody (ANA) criterion (whose results are crucial for classifying SLE-negative cases) exhibited favorable sensitivity 0.78 ± 0.09 (95% confidence interval) and a positive predictive value 0.85 ± 0.08 but a marginal performance for specificity 0.60 ± 0.11 and uncertain predictivity for the negative predictive value 0.48 ± 0.11. Averaged over the remaining 21 criteria, these four performance metrics were 0.69 ± 0.11, 0.87 ± 0.04, 0.54 ± 0.10, and 0.93 ± 0.03. Conclusions: ANA performance statistics imply that genAI yields confident assessments of SLE negativity (per high sensitivity) but weaker positivity. The remaining genAI criterial determinations support (per specificity) confident assertions of SLE-positivity but tend to misclassify a significant fraction of clinical positives as UCTD. Full article

Objective: This study aims to evaluate obstetric and neonatal outcomes in pregnancies complicated by RDs and to identify hemogram-derived biomarkers associated with adverse perinatal events. Methods: This retrospective cohort study analyzed 360 pregnancies in individuals diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), Sjögren’s disease, sarcoidosis, undifferentiated connective tissue disease (UCTD), and other autoimmune conditions, followed up at the Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, between 2013 and 2018. Data on disease activity, maternal complications, neonatal outcomes, and inflammatory markers were extracted from electronic medical records. Results: Patients with SSc had the highest rates of preterm birth (57.1%) and fetal growth restriction (FGR) (42.9%), whereas those with SLE (50%) and AS (25%) exhibited the highest disease flare rates. Neonates born to mothers with SSc, SLE, and Sjögren’s disease had significantly lower Apgar scores, suggesting increased neonatal distress. NICU admission was associated with elevated neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR), with higher NLR and ELR also predicting spontaneous abortion. Monocyte-to-lymphocyte ratio (MLR) and ELR demonstrated the highest predictive value for composite adverse perinatal outcomes. Additionally, RA patients experiencing disease flares had an 87.5% cesarean section (CS) rate, significantly exceeding the general population rate. Conclusions: This study underscores the increased risk of preterm birth, FGR, and neonatal complications in RD pregnancies, particularly in SSc and SLE patients. The findings suggest that early risk assessment using hemogram-based inflammatory markers may improve perinatal management and patient stratification. Full article

Background: Aminaphtone is a well-established pharmaceutical agent that has been utilized for over 40 years, primarily due to its effectiveness in treating microvascular disorders. Recent studies have explored its impact on various conditions, including chronic venous insufficiency, diabetic microangiopathy, leg ulcers, systemic sclerosis, and Raynaud’s phenomenon. These investigations have consistently demonstrated that aminaphtone enhances skin blood perfusion and mitigates endothelial damage, all while maintaining a robust safety profile over time. Case Summary: This report highlights the potential of aminaphtone in improving microcirculation in a young patient who experienced spontaneous capillary rupture in her second finger. A 38-year-old woman with undifferentiated connective tissue disease presented to the clinic for periungual videocapillaroscopy (NVC). Given the microangiopathic changes observed during the NVC, she was prescribed aminaphtone. After seven months of treatment, a follow-up NVC revealed significant improvement in the capillaroscopic findings. A comprehensive literature review on aminaphtone was conducted using electronic databases (PUBMED, Google Scholar, ResearchGate, UpToDate), along with manual searches, focusing on articles published until November 2024. Conclusion: Treatment with aminaphtone led to notable improvements in microangiopathic health. Following the introduction of this medication, the nailfold microvascular bed, which previously exhibited severe alterations, showed a remarkable transition to only mild abnormalities. Full article

Background: Antibodies against Ku have been described in patients with various connective tissue diseases. The objective of this study was to describe the clinical, functional, and imaging characteristics of interstitial lung disease in patients with anti-Ku antibodies. Methods: This single-center, retrospective observational study was conducted at a tertiary referral institution. Patients with positive anti-Ku antibodies and interstitial lung disease identified between 2007 and 2022 were included. Clinical, immunological, functional, and imaging data were systematically reviewed. Results: Nineteen patients (ten females) with a mean age of 59 ± 12.6 years were included. The most frequent associated diagnosis was systemic sclerosis (42%), followed by rheumatoid arthritis (26%), Sjögren syndrome, undifferentiated connective tissue disease, and overlap between systemic sclerosis and idiopathic inflammatory myopathy (scleromyositis). Imaging revealed frequent septal and intralobular reticulations and ground-glass opacities, with nonspecific interstitial pneumonia as the predominant pattern (53%). The mean forced vital capacity was 82% ± 26 of the predicted value, and the mean diffusing capacity for carbon monoxide was 55% ± 21. Over the first year of follow-up, the mean annual forced vital capacity decline was 140 mL/year (range: 0–1610 mL/year). The overall survival rate was 82% at 5 years and 67% at 10 years. Conclusions: Most patients with interstitial lung disease and anti-Ku antibodies presented with dyspnea, a mild-to-moderate restrictive ventilatory pattern, and reduced diffusing capacity for carbon monoxide. The CT pattern was heterogeneous but was consistent with nonspecific interstitial pneumonia in half of the patients. Full article

Background: Dental pulp (DP) is a connective tissue composed of various cell types, including fibroblasts, neurons, adipocytes, endothelial cells, and odontoblasts. It contains a rich supply of pluripotent stem cells, making it an important resource for cell-based regenerative medicine. However, current stem cell collection methods rely heavily on the enzymatic digestion of dissected DP tissue to isolate and propagate primary cells, which often results in low recovery rates and reduced cell survival, particularly from deciduous teeth. Methods: We developed a novel and efficient method to obtain a sufficient number of cells through a one-step cultivation process of isolated DP. After the brief digestion of DP with proteolytic enzymes, it was scratched onto a culture dish and cultured in a suitable medium. By day 2, the cells began to spread radially from DP, and by day 10, they reached a semi-confluent state. Cells harvested through trypsinization consistently yielded over 1 million cells, and after re-cultivation, the cells could be propagated for more than ten passages. Results: The proliferative and differentiation capacities of the cells after the 10th passage were comparable to those from the first passage. The cells expressed alkaline phosphatase as an undifferentiation marker. Similarly, they also maintained the constitutive expression of stem cell-specific markers and differentiation-related markers, even after the 10th passage. Conclusions: This method, termed “scratch-based isolation of primary cells from human dental pulps (SCIP)”, enables the efficient isolation of a large number of DP cells with minimal equipment and operator variability, while preserving cell integrity. Its simplicity, high success rate, and adaptability for patients with genetic diseases make it a valuable tool for regenerative medicine research and clinical applications. Full article

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene–disease associations and protein–protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial–mesenchymal plasticity. Full article

(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed. Full article

The introduction of the so-called immune checkpoint inhibitors (ICIs) substantially changed the history of cancer therapy. On the other hand, they can induce the development of rheumatic immune-related adverse events (Rh-irAEs). In the scenario of a joint oncology/rheumatology outpatient clinic, we conducted a single-centre descriptive study to define from a laboratory, clinical and therapeutic point of view, rheumatic conditions developed during anti-PD1 treatment. The study included 32 patients (M/F 16/16, median age 69, IQR 16.5). According to the international classification criteria, eight patients could be classified as affected by Rheumatoid Arthritis, one by Psoriatic Arthritis, six by Polymyalgia Rheumatica, five by systemic connective tissue diseases (two systemic lupus erythematosus, two Sjögren’s syndrome, one undifferentiated connective tissue disease). The remaining patients were diagnosed as having undifferentiated arthritis or inflammatory arthralgia. The median interval between ICIs starting and the onset of symptoms was 14 weeks (IQR 19.75). Moving to treatment, the longitudinal observation revealed that all RA, PsA and CTD patients required the introduction of treatment with DMARDs. In conclusion, the growing use of ICIs in a real-life setting confirmed the possible development of different rheumatological conditions, further emphasising the need for shared oncology/rheumatology management. Full article

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment’s efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was −0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline. Full article

Background: The presence of Antinuclear antibodies/Dense Fine Speckled 70 (ANA/DFS70) has been proposed as a negative biomarker in the process of exclusion of systemic autoimmune/autoinflammatory rheumatic diseases (SARD). The purpose was to evaluate and characterize ANA/DFS70 patients in a large Colombian population with SARD; rheumatoid arthritis (RA), Psoriasis (PsO), Undifferentiated connective tissue disease (UCTD), first-degree relatives of (FDR), and healthy controls (HC). Methods: ANA determination was performed using indirect immunofluorescence. Samples with positive dense fine granular staining in the nucleoplasm of the interphase cell (AC2) fluorescence were confirmed with CytoBead/ANA and ANA/modified (Knocked out for the PSPI1 gen). Results: 530 mestizo Colombian participants were included. ANA/DFS70 antibody positivity in the whole group was 2.3%, and 0.8% in SARD; no RA patients were positive. ANA/DFS70 positives in UCTD were three women; the average time of evolution of the disease was 9.4 years. The most frequent clinical findings were arthralgias, non-erosive arthritis, and Raynaud’s phenomenon. The PsO positive was a woman with C-reactive protein (CRP) positivity and a negative erythrocyte sedimentation rate (ESR) without any other positive autoantibody or extracutaneous manifestation. FDR and HC positives were 7/8 women. All were negative for other autoantibodies. Conclusions: ANA/DFS70 autoantibodies were present in Colombian patients with SARD at a shallow frequency, they were more prevalent in healthy individuals. Full article

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least two consecutive determinations, for one or more aPL [anti-Cardiolipin (aCL) IgM/IgG, anti-Beta2Glycoprotein I (aB2GPI) IgM/IgG, Lupus Anticoagulant (LA)]. All subjects were evaluated every six months, or in accordance with the patient’s clinical course, in order to record the development of clinical and laboratory features suggestive for sAD. Ninety-five subjects [M/F 20/75, median age at first determination 46 years, Interquartile Range (IQR) 19] were enrolled. Thirty-three subjects (34.7%) were positive for only one aPL [15 (15.8%) for aCL, 15 (15.8%) for LA, and 5 (5.3%) for aB2GPI]; 37 (38.9%) had double positivity [32 (33.6%) for aCL and aB2GPI; 5 (5.3%) for aCL and LA], 23 (24.2%) had triple positivity. We prospectively followed up our cohort for a median period of 72 months (IQR 84). During a total follow-up of 7692 person-months, we found an absolute risk for sAD development equal to 1.8%. Specifically, 14 (14.7%) patients developed a sAD: in four patients (4.2%), after developing a thrombotic event, an antiphospholipid syndrome was diagnosed, 7 (7.4%) patients developed an Undifferentiated Connective Tissue Disease after a median period of 76 months (IQR 75.5), and lastly, three (3.1%) patients could be classified as affected by Systemic Lupus Erythematosus according to the ACR/EULAR 2019 criteria. The presence of triple positivity status resulted in being significantly associated with the progression to sAD (p-value = 0.03). In conclusion, we observed the development of sAD in almost 15% of aPL positive subjects. Triple positivity was significantly associated with this progression, suggesting a possible role as biomarker for this condition. Thus, our results could suggest the need for periodic follow-up for such patients to assess early diagnosis and treatment. Full article

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis. Full article

Rheumatologists in Europe and the USA increasingly rely on fluorescence optical imaging (FOI, Xiralite) for the diagnosis of inflammatory diseases. Those include rheumatoid arthritis, psoriatic arthritis, and osteoarthritis, among others. Indocyanine green (ICG)-based FOI allows visualization of impaired microcirculation caused by inflammation in both hands in one examination. Thousands of patients are now documented and most literature focuses on inflammatory arthritides, which affect synovial joints and their related structures, making it a powerful tool in the diagnostic process of early undifferentiated arthritis and rheumatoid arthritis. However, it has become gradually clear that this technique has the potential to go even further than that. FOI allows visualization of other types of tissues. This means that FOI can also support the diagnostic process of vasculopathies, myositis, collagenoses, and other connective tissue diseases. This work summarizes the most prominent imaging features found in FOI examinations of inflammatory diseases, outlines the underlying anatomical structures, and introduces a nomenclature for the features and, thus, supports the idea that this tool is a useful part of the imaging repertoire in rheumatology clinical practice, particularly where other imaging methods are not easily available. Full article