Systemic Autoimmune Rheumatic Diseases Research Articles

Periconceptional Counselling in Women with Autoimmune Inflammatory Rheumatic Diseases

Systemic autoimmune rheumatic diseases (SARDs) in pregnancy represent a complex challenge for both patients and healthcare providers. Timely preparation for pregnancy enables adequate disease control, thereby reducing the risk of disease flare and pregnancy complications. Interdisciplinary care starting from the pre-pregnancy period throughout pregnancy and during breastfeeding ensures better fetal and maternal outcomes. This review provides a comprehensive guide to pre-pregnancy counselling in SARDs, an overview of medication management strategies tailored to pregnancy, disease activity and pregnancy monitoring in patients, and the promotion of shared decision making between healthcare providers and patients. Guidelines from international organizations were selected to provide a basis for this review and guidance through the quintessential discussion points of care.

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope

Diagnostic Approach to Interstitial Lung Diseases Associated with Connective Tissue Diseases.

Interstitial lung disorders are a group of respiratory diseases characterized by interstitial compartment infiltration, varying degrees of infiltration, and fibrosis, with or without small airway involvement. Although some are idiopathic (e.g., idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias, and sarcoidosis), the great majority have an underlying etiology, such as systemic autoimmune rheumatic disease (SARD, also called Connective Tissue Diseases or CTD), inhalational exposure to organic matter, medications, and rarely, genetic disorders. This review focuses on diagnostic approaches in interstitial lung diseases associated with SARDs. To make an accurate diagnosis, a multidisciplinary, personalized approach is required, with input from various specialties, including pulmonary, rheumatology, radiology, and pathology, to reach a consensus. In a minority of patients, a definitive diagnosis cannot be established. Their clinical presentations and prognosis can be variable even within subsets of SARDs.

Imaging Innovations in the Screening, Diagnosis, and Monitoring of Systemic Autoimmune Disease-Related Interstitial Lung Disease

Interstitial lung disease (ILD) is a common and serious complication of systemic autoimmune rheumatic diseases (SARD). The prevalence and prognosis of ILD vary depending on the type and severity of the underlying SARD. Recently, two drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ILD in SARD, and the American College of Rheumatology (ACR) has issued guidelines for the screening and monitoring of these patients. Therefore, it is essential to detect and manage ILD in SARDs as early as possible. High-resolution CT of the chest is the current gold standard test for diagnosis of ILD, yet, it is not uniformly performed as an initial diagnostic test. This review discusses the latest advances in imaging techniques for the diagnosis, assessment, and follow-up of SARD-ILDs.

Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study.

This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Dermatomyositis (DM), Polymyositis (PM) or Sjogren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. This population-based cohort study revealed that patients diagnosed with SLE, SS and DM had significantly higher risks of developing mental illness when compared with patients with RA.

Antinuclear antibody (ANA) positivity pattern by line immunoassay in a hospital from eastern India: Update from a laboratory perspective

ABSTRACT Context: The existence of more than one antibody in systemic autoimmune rheumatic diseases (SARDs) or connective tissue disease (CTD) along with features of more than one autoimmune disease (AD) in an individual is suggestive of overlap syndrome (OS). Line immunoassay (LIA) can target many autoantibodies in a single approach, thus making the identification of OS feasible. Aims and Objectives: This study aimed to identify the pattern of distribution of antinuclear antibodies by LIA prevalent in a hospital population in eastern India and identify common forms of SARD in this belt based on laboratory findings. Material and Methods: A total of 1660 samples received for ANA profile testing by LIA were analysed. Statistical Analysis: Factor analysis was performed with factor loading scores used in the k-means algorithm to identify clustering of various autoantibodies. Results: U1-snRNP positivity was the highest at 16.69%, and the least frequent autoantibody noted was anti-Jo-1 at 0.71% positivity. Based on the outcome of factor analysis, three clusters were determined. Cluster 1 showed a predominance of anti-PM/Scl antibodies, cluster 2 showed a predominance of anti-dsDNA, anti-histone, anti-SmD1, anti-nucleosomes, anti-PCNA, anti-Po, anti-SSA/Ro52, anti-SSA-Ro60, anti-SSB/La, anti-Scl-70, anti-Mi-2, anti-Ku and anti-AMA-M2, and cluster 3 showed a predominance of anti-U1-snRNP. Conclusions: Mixed connective tissue disease (MCTD) and overlap syndrome (OS) are prevalent more than pure form of an AD in our study population. OS may be missed out by monospecific immunoassays and hence adds to diagnostic challenges. LIA may be more useful in identifying specific autoantibodies by a single approach rather than monospecific immunoassays in populations after a positive screen by indirect immunofluorescence (IIF).

Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.

Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients. We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis. A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs. The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.

Factors Associated With an Electronic Health Record-Based Definition of Postacute Sequelae of COVID-19 in Patients With Systemic Autoimmune Rheumatic Disease.

Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

Fully automated chemiluminescence microarray immunoassay for detection of antinuclear antibodies in systemic autoimmune rheumatic diseases

Abstract Objectives Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention. Methods A CLMIA method that can detect 14 kinds of antinuclear antibodies was established and optimized. Basic performance and diagnostic performance of CLMIA was evaluated by comparing it with line immunoassay (LIA) and indirect immunofluorescence (IIF). Results Through conditional exploration, the optimal blocking time and blocking temperature were determined to be 18 h and 25 °C, respectively. The enzyme-labeled secondary antibody reaction concentration was 0.1 μg/mL, the incubation temperature of serum and enzyme-labeled secondary antibody were 30 °C, and the incubation time of serum and enzyme-labeled secondary antibody were 40 min. After parameter optimization, CLMIA demonstrated high accuracy with a relative bias <15 %; high sensitivity with detection limits below 3 IU/mL for dsDNA and below 1 RU/mL for other ANAs; and high reproducibility with both intra-assay and inter-assay coefficients of variation (CV) <15 %.The CLMIA detection method established in this study was also demonstrated to have good clinical diagnostic performance, showing the highest area under curve (AUC=0.87, p=0.042 and p=0.03). The CLMIA and LIA revealed substantial to good agreements on specific antinuclear antibodies except anti-dsDNA, with the Cohen’s kappa from 0.72 to 0.89. Samples that produced discrepant results between the CLMIA and LIA methods were further analyzed. Upon additional testing, most of these samples were ultimately determined to have been correctly detected by the CLMIA assay rather than the LIA assay, suggesting that CLMIA also shows some superiority in diagnosing dsDNA. Conclusions The CLMIA could become a potential routine method for detecting ANAs with the advantages of good detection performance.

Insight into the Epidemiology of the Adult-onset Systemic Autoimmune Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients.

Although systemic autoimmune rheumatic diseases (SARDs) seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity of data compared with the developed countries. Furthermore, most of the studies addressed a particular disease. This work aimed to shed light on the relative frequency and epidemiology of the different adult-onset SARDs in Egypt. This is a retrospective hospital-based study including six university hospitals providing free health care services: Cairo, Alexandria, Tanta, Ismailia, Beni-Suef and Assiut University Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient departments between January 2000 and December 2021 were retrospectively reviewed. Data about the patient's diagnosis, gender, age at disease onset, year of disease onset and residence were collected. The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behçet's disease (BD) and spondyloarthropathies (SPA) represented the main SARDs in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect females; males are mainly affected by axial SPA and BD. There is an increasing incidence of SARDs during the study period. The study revealed the high burden of SARDs in Egypt, helping better allocation of economic resources for the management of diseases of the highest prevalence and those affecting the young reproductive age groups. Increased public and medical staff awareness about SARDs is recommended to help early referral of patients to rheumatologists and, hence, better estimation of their epidemiology.

Novel multiclass classification machine learning approach for the early-stage classification of systemic autoimmune rheumatic diseases.

Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators. A total of 925 SARDs patients were included, categorised into SLE, Sjögren's syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model. Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles. This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.

Associations of DMARDs with post-acute sequelae of COVID-19 in patients with systemic autoimmune rheumatic diseases: a prospective study

Abstract Objective We investigated the baseline DMARD use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs). Methods Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after a positive PCR/antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate the odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection. Results We analysed 510 patients with SARDs and COVID-19 from 11 March 2021 to 17 June 2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs conventional synthetic DMARD (csDMARD) users [adjusted OR (aOR) 2.69 (95% CI 1.23, 5.88)]. IL-12/23, IL-17A or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC [aOR 3.03 (95% CI 1.08, 8.49)]. CD20i users had significantly fewer symptom-free days vs csDMARD users [aOR −4.12 (95% CI −7.29, −0.94)]. Conclusion CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai and IL-23i with PASC calls for additional study.

404. Impact of cross-coronavirus humoral immunity in post-acute sequelae of COVID-19 in systemic autoimmune rheumatic diseases patients

Abstract Background Beyond the acute illness caused by SARS-CoV-2, about one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. Methods To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using Systems Serology in two independent cohorts of patients with pre-existing systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. Results A distinct qualitative shift observed in Fcγ receptor binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly stronger Fcγ receptor binding antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an OC43 S2-specific antibody response with stronger Fcγ-receptor binding, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. Conclusion These findings from two independent cohorts implicate previous common Coronavirus imprinting as a marker for the development of PASC in individuals with SARDs. Disclosures Douglas A. Lauffenburger, PhD, Sanofi: Board Member|Sanofi: Honoraria|Sanofi: Honoraria Zachary Wallace, MD, MSc, Bristol-Myers Squibb: Grant/Research Support|Horizon: Advisor/Consultant|MedPace: Advisor/Consultant|Principia/Sanofi: Grant/Research Support|Sanofi: Advisor/Consultant|Shionogi: Advisor/Consultant|Viela Bio: Advisor/Consultant|Zenas BioPharma: Advisor/Consultant Jeffrey Sparks, MD, AbbVie: Advisor/Consultant|Amgen: Advisor/Consultant|Boehringer Ingelheim: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|Bristol Myers Squibb: Grant/Research Support|Gilead: Advisor/Consultant|Inova Diagnostics: Advisor/Consultant|Janssen: Advisor/Consultant|Optum: Advisor/Consultant|Pfizer: Advisor/Consultant Galit Alter, PhD, Leyden Labs: Ownership Interest|Moderna Therapeutics: Employee|Seromyx Systems: Ownership Interest

Posttraumatic stress disorder symptoms in systemic autoimmune rheumatic disease patients during the early COVID-19 pandemic.

Given reports of increased prevalence of PTSD symptoms at COVID-19 pandemic onset, we aimed to assess the prevalence of posttraumatic stress disorder (PTSD) symptoms at pandemic onset in individuals with and without systemic autoimmune rheumatic disease (SARD). In May 2020, we invited 6678 patients to complete the Brief Trauma Questionnaire and the Posttraumatic Stress Disorder Checklist (PCL-5), validated PTSD symptom screenings. We compared responses from patients with and without SARD using multivariable logistic regression. We received 1473 responses (22% response rate) from 5/2020 to 9/2021 (63 with prior PTSD diagnoses, 138 with SARD history). The SARD population was more female (p .0001) and had a higher baseline prevalence of stress disorders (56% vs. 43%, p .004). SARD subjects reported more experiences with life-threatening illness, 60%, versus 53% among those without SARD (p .13), and more antidepressant or anxiolytic medication use pre-pandemic (78% vs. 59%, p .0001). Adjusting for pre-pandemic PTSD diagnosis, younger age and history of stress disorder were the most significant predictors of PCL-5 positivity. There were no significant differences in PCL-5 score or positivity among those with or without SARD. In this population, patients with SARD had a higher pre-COVID-19 prevalence of stress-related conditions, but it was not the case that they had an increased risk of PTSD symptoms in the early pandemic. Younger individuals, those with baseline depression, anxiety, or adjustment disorders, and those taking antidepressant or anxiolytic medications were more likely to have PTSD symptoms in the first waves of the COVID-19 pandemic.

Effectiveness of a fourth dose of COVID-19 mRNA vaccine in patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs: an emulated target trial

Patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs (DMARDs) might have blunted responses to COVID-19 vaccines. The initial mRNA vaccine series is defined as three doses for this population and a fourth booster dose is recommended. The effectiveness of the fourth dose in patients with systemic autoimmune rheumatic diseases using DMARDs is not well established. We aimed to assess the effectiveness of receiving versus not receiving a fourth dose of COVID-19 mRNA vaccine using a target trial framework, in a cohort of patients with systemic autoimmune rheumatic diseases receiving DMARD therapy. We conducted an emulated target trial using observational data from the Mass General Brigham health-care system to compare receiving versus not receiving a fourth mRNA vaccine dose. Analysed patients had systemic autoimmune rheumatic diseases, were prescribed DMARDs, and were eligible for a fourth dose of BNT162b2 or mRNA-1273 vaccines between Jan 16 and June 11, 2022. To account for temporal changes, the study period was divided into 1-week intervals. Fourth-dose-exposed patients were included in a 1-week interval if they received a fourth mRNA dose in that interval; fourth-dose-unexposed patients were eligible for but had not received the fourth dose of the vaccine. The primary outcome was a SARS-CoV-2 infection; the secondary outcome was severe SARS-CoV-2 infection (ie, admission to hospital or death within -3 to +14 days of a positive test). We assessed the effectiveness of the fourth dose using time-stratified, overlap propensity score-weighted Cox regression models. We included 4305 patients, 3126 of whom received a fourth dose of vaccine and 1179 who had not. The median follow-up time was 135 days (IQR 112-154) among patients who had received a fourth dose and 65 days (30-156) among patients who had not received a fourth dose. After overlap weighting in both groups, 1863 (72·7%) of 2563 participants were women, 700 (27·3%) were men, and 2242 (87·5%) were White. Rheumatoid arthritis was present in 1392 (54·3%) of 2563 participants; the most frequent treatments were conventional synthetic DMARDs (1489 [58·1%]) or biological DMARDs (1007 [39·3%]). SARS-CoV-2 infection risk was lower among patients receiving versus not receiving a fourth dose of vaccine (HR 0·59 [95% CI 0·47-0·74]). A fourth dose reduced the risk of admission to hospital or death within -3 to +14 days of SARS-CoV-2 infection (0·35 [0·14-0·85]). In this emulated target trial, a fourth dose of COVID-19 mRNA vaccine reduced the risk of SARS-CoV-2 infection and severe COVID-19 among patients with systemic autoimmune rheumatic diseases using DMARDs during the Omicron era. Patients with systemic autoimmune rheumatic diseases should be encouraged to remain up-to-date with COVID-19 vaccinations. The National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Effectiveness of a fourth mRNA dose among individuals with systemic autoimmune rheumatic diseases during the Omicron era

Effectiveness of a fourth mRNA dose among individuals with systemic autoimmune rheumatic diseases during the Omicron era

The Role of Anti-DFS70 in the Diagnosis of Systemic Autoimmune Rheumatic Diseases

The diagnosis of systemic autoimmune rheumatic disease (SARD) or its exclusion is carried out taking into account the results of immunological studies, primarily antinuclear antibodies (ANA) and specific autoantibodies. Often, during ANA analysis via indirect immunofluorescence reaction on cellular and tissue substrates, a dense fine speckled 70 (DFS70) fluorescence pattern is observed. Studies on the diagnostic significance of antibodies to anti-DFS70 allow for optimizing the stepwise diagnosis of SARD. Currently, a two-step strategy for laboratory diagnostic investigation is recommended: in the first step, ANA screening is performed, and in the second step, patients with positive results undergo confirmatory tests to detect specific antibodies against individual nuclear antigens. The detection of anti-DFS70 in ANA-seropositive patients without clinical and/or other specific serological markers characteristic of a particular disease within the SARD group may be considered a negative prognostic marker. Also, in the process of decision making in clinical practice, we should remember that anti-DFS70 can be found in the blood of patients with a different, non-SARD pathology and that most people showing anti-DFS70 are healthy individuals.

Ovarian dysfunction in adolescent girls with autoimmune rheumatic diseases

ObjectiveTo explore the different menstrual and pubertal abnormalities in adolescent females with systemic autoimmune rheumatic diseases (ARD).MethodsThe study included adolescent girls aged 13–18 years with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE), and juvenile dermatomyositis (JDM) classified according to their international classification criteria. Data were collected from our patients’ files and interpreted with respect to the demographic, clinical, disease assessment parameters, medications used, and the hormonal profile. The aspects of puberty and menstruation were assessed by a gynaecologist with ultrasound evaluation as well. The girls were classified according to their menstrual pattern into those with regular cycles versus abnormal ones. The subgroups were compared and significant variables entered into a logistic regression model to detect the independent predictors.ResultsTwenty-one girls with JSLE were included, besides 23 JIA and 8 JDM cases. Ten patients with JSLE (47.6%) had menstrual abnormalities, whereas only four JIA (17.4%) and 1 JDM girls had these alterations without significant difference between the three groups. The median of the SLICC/ACR damage index was statistically higher in JSLE with abnormal menstrual cycles, similarly were the cumulative steroid dose and puberty onset. No difference was observed between JIA or JDM subgroups concerning the disease parameters, hormonal profile, ultrasound assessment or the treatment lines. The most significant predictor for menstrual abnormalities in JSLE was the SLICC/ACR damage index.ConclusionMenstrual abnormalities is a common disturbance among adolescent girls with ARDs. The SLICC/ACR damage index is the main determinant for menstrual abnormalities rather than the cumulative steroid use or disease duration in JSLE.

Discriminating between Homogeneous (AC-1) and Dense Fine Speckled (AC-2) Antinuclear Antibody Patterns: Re-Evaluation of Immunofluorescence Imaging.

Antinuclear antibodies (ANAs) are essential diagnostic markers in systemic autoimmune rheumatic diseases. Among the 30 ANA patterns, homogeneous (AC-1) and dense fine speckled (AC-2) should be focused on owing to their somewhat indistinct presentation in immunofluorescence imaging and distinct correlation with clinical conditions. This study aimed to develop a flowchart to guide discrimination between AC-1 and AC-2 patterns and to re-evaluate ANA samples according to this flowchart to verify its detection ability. We re-evaluated immunofluorescence imaging of 62 ANA blood samples simultaneously subjected to solid-phase assays for autoantibodies against dsDNA, nucleosomes, histones, and DFS70. The results showed statistically significant odd ratios (ORs) of detection of anti-DFS70 using AC-2 after re-evaluation of total samples (OR 101.9, 95% CI 11.7-886.4, p-value < 0.001) and subgroup analysis of patients' samples (OR 53.8, 95% CI 5.9-493.6, p-value < 0.001). The OR of anti-nucleosome/histone/dsDNA detection using AC-1 in re-evaluated data increased to 5.43 (95% CI 1.00-29.61, p-value = 0.05). In the analysis of specific autoantibodies, more than half of the samples with an AC-2 pattern (54.2%) had specific autoantibodies other than anti-DFS70. We conclude that the flowchart for discriminating between AC-1 and AC-2 ANA patterns in this study is a viable practical guide for other laboratories when encountering equivocal ANA results.

Risk factors and outcomes for repeat COVID-19 infection among patients with systemic autoimmune rheumatic diseases: A case-control study

ObjectiveTo investigate risk factors and outcomes of repeat COVID-19 infections among patients with systemic autoimmune rheumatic diseases (SARDs). MethodsWe performed a case-control study investigating repeat COVID-19 infection within the Mass General Brigham Health Care System. We systematically identified all SARD patients with confirmed COVID-19 (15/Mar/2020 to 17/Oct/2022). Cases had confirmed repeat COVID-19 infections >60 days apart (index date: repeat COVID-19 date). Controls were matched to cases (up to 3:1) by calendar date of first infection and duration between first COVID-19 infection and index dates. We collected demographics, lifestyle, comorbidities, SARD features, and COVID-19 characteristics at initial infection and index date by medical record review. We used conditional logistic regression to identify associations with repeat COVID-19 infection, adjusting for potential confounders. We described the severity of repeat COVID-19 infection among cases. ResultsAmong 2203 SARD patients with COVID-19, we identified 76 cases with repeat COVID-19 infection (80.3 % female) and matched to 207 matched controls (77.8 % female) with no repeat infection. At first infection, cases were younger (mean 49.5 vs. 60.3 years, p < 0.0001), less likely to have hypertension (32.9 % vs. 45.9 %, p = 0.050), and less likely to have been hospitalized for COVID-19 (13.2 % vs. 24.6 %, p = 0.037) than controls. At index date, cases were more likely than controls to be rituximab users (18.4 % vs. 6.3 %, p = 0.0021). In the multivariable model, younger age (OR 0.67 per 10 years, 95 %CI 0.54–0.82), rituximab use vs. non-use (OR 3.38, 95 %CI 1.26–9.08), and methotrexate use vs. non-use (OR 2.24, 95 %CI 1.08–4.61) were each associated with repeat COVID-19 infection. Among those with repeat COVID-19 infection, 5/76 (6.6 %) were hospitalized and there were no deaths. ConclusionYounger age, rituximab, and methotrexate were each associated with repeat COVID-19 infection risk among patients with SARDs. Reassuringly, there were no deaths, and the hospitalization rate was low among those with repeat COVID-19 infection.