Autoimmune Rheumatic Diseases Research Articles

Autoimmune rheumatic transitional care model development

AimTo develop a transitional care model for autoimmune rheumatic disease patients based on the needs analysis.MethodMixed Method, Explanatory sequential design (QUAN-qual) has been conducted. Quantitative data were collected through medical record and structured interviews. Qualitative study has been done through Focused Group Discussion (FGD), based on problems met in previous quantitative study. We have done the coding processed, followed by determining categories and themes to reach the intercoder agreement with peer-debriefing. Analysis of the final results of research was assisted by the external auditor to form a model of care.ResultThe quantitative data collection from 27 patients showed that the transition age was 18–19 year-old, age of onset 4–17 year-old, 23 patients (85, 2%) with SLE, 4 patients (14.8%) with JIA. Two patients (7.4%) had different diagnosis from the pediatric clinic, 1 patient (3.7%) had no diagnosis from previous clinic. Drug switching during transition occurred in 14 patients (51.9%) and 3 patients (11.1%) has no known medication history. Data regarding disease activity at initial diagnosis were not available in 26 patients (96.3%). The combined FGD analysis found several key words related to “the need of change” in RSCM autoimmune rheumatic transitional care.ConclusionA development of transitional care model for autoimmune rheumatic disease consist of documents about service algorithm, transfer documents, systematic work protocols with education check list has been done.

EBNA-1 antibody and autoimmune rheumatic diseases: A Mendelian Randomization Study

BackgroundNumerous studies have investigated a possible correlation between Epstein-Barr virus (EBV) and autoimmune rheumatic diseases (ARDs). However, establishing a cause-and-effect relationship remains a challenging endeavor. This study employs Mendelian randomization to examine the impact of EBV nuclear antigen-1 antibody (EBNA-1) antibody levels on the susceptibility to nine distinct ARDs, including rheumatoid arthritis (RA), primary Sjogren's syndrome (PSS), systemic lupus erythematosus (SLE), undifferentiated reactive arthritis (UA), systemic sclerosis (SSc), adult-onset Still's disease (AOSD), psoriatic arthritis (PsA), dermatomyositis (DM), and ankylosing spondylitis (AS). MethodsThe researchers applied a two-sample Mendelian randomization approach, utilizing online data from separate cohorts of European descent. We drew upon data from GWAS related to EBNA-1 antibody levels and the nine autoimmune-related disorders. Our primary analyses predominantly relied on the Inverse Variance Weighted methodology, complemented by a range of sensitivity assessments. ResultsOur analysis revealed significant direct associations between EBNA-1 antibody levels and the risk of developing PSS (95 % CI: 0.44 to 0.85, p = 0.003), PsA (95 % CI: 0.36 to 0.99, p = 0.044), AS (95 % CI: 0.07 to 0.88, p = 0.031), and UA (95 % CI: 0.56 to 0.96, p = 0.025). These results remained consistent through comprehensive sensitivity analyses. However, no clear associations were found for the other specified conditions. ConclusionsOur findings provide compelling evidence that EBNA-1 antibody levels play a role in developing ARDs. These findings enhance our understanding of ARD pathogenesis and hold substantial promise for developing potential treatment strategies.

Treatment of interstitial lung disease in systemic sclerosis: guidelines and new clinical trial results.

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The American College of Rheumatology (ACR), in conjunction with the American College of Chest Physicians (CHEST), recently published clinical practice guidelines for the treatment of adults with systemic autoimmune rheumatic disease-associated ILD, including SSc-ILD. Herein, we summarize evidence from randomized trials evaluating the safety and efficacy of pharmacologic therapies for the treatment of SSc-ILD. In this review, we present findings from recent randomized controlled trials in SSc-ILD. The pharmacologic therapies discussed include immunosuppressive medications (mycophenolate, cyclophosphamide, rituximab, and tocilizumab) and antifibrotic medications (nintedanib and pirfenidone). Randomized trials provide an evidence base for the SSc-ILD treatment recommendations put forth in the ACR/CHEST Guidelines for the treatment of ILD in people with systemic autoimmune rheumatic diseases. These guidelines will help inform clinical practice and highlight areas in which further research is needed.

The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases-An Observational High-Resolution Magnetic Resonance Imaging Study.

Autoimmune rheumatic diseases (AIRD) can cause intracranial artery stenosis (ICAS) and lead to stroke. This study aimed to characterize patients with ICAS associated with AIRD. Utilizing data from a high-resolution magnetic resonance imaging (HRMRI) database, we retrospectively reviewed AIRD patients with ICAS. Stratification into vasculitis, atherosclerosis, and mixed athero-vasculitis subtypes was based on imaging findings, followed by a comparative analysis of clinical characteristics and outcomes across these subgroups. Among 139 patients (45.1±17.3 years; 64.7% females), 56 (40.3%) were identified with vasculitis, 57 (41.0%) with atherosclerosis, and 26 (18.7%) with mixed athero-vasculitis. The average interval from AIRD-onset to HRMRI was 5 years. Patients with vasculitis presented with a younger age of AIRD-onset (34.5±19.4 years), nearly ten years earlier than other groups (P=0.010), with a higher artery occlusion incidence (44.6% vs. 21.1% and 26.9%, P=0.021). Patients with atherosclerosis showed the highest cardiovascular risk factor prevalence (73.7% vs. 48.2% and 61.5%, P=0.021) but lower intracranial artery wall enhancement instances (63.2% vs. 100% in others, P<0.001). The mixed athero-vasculitis group, predominantly male (69.2% vs. 30.4% and 25.6%, P<0.001), exhibited the most arterial involvement (5 arteries per person vs. 3 and 2, P=0.001). Over an average 21-month follow-up, 23 (17.0%) patients experienced stroke events, and 8 (5.9%) died, with the mixed athero-vasculitis group facing the highest risk of stroke events (32.0%) and the highest mortality (12.0%). Intracranial arteries are injured and lead to heterogeneous disease courses when exposed to AIRD and cardiovascular risk factors. While atherosclerosis acceleration is common, vasculitis may further contribute to early-developed occlusion and multiple artery involvement. Varied intracranial arteriopathies may result in different outcomes. ICAS = intracranial artery stenosis; AIRD = Autoimmune rheumatic diseases; HRMRI = high-resolution magnetic resonance imaging.

Clinical Characteristics, Prognostic Factors, and Outcomes of COVID-19 in Autoimmune Rheumatic Disease Patients: A Retrospective Case-Control Study from Astana, Kazakhstan.

Background: Viral infections, including coronavirus disease 2019 (COVID-19), in patients with autoimmune rheumatic diseases (AIRDs) tend to present more severe disease. This study aims to investigate the clinical characteristics and risk factors for severe infection in rheumatologic patients. Methods: We included patients with a diagnosis of AIRD and COVID-19 infection between January 2022 and July 2023. Patients with AIRDs infected with SARS-CoV-2 were matched with control patients of the general population according to age (±5 years) and sex in a 1:1 ratio. Confirmed infection was defined if a patient had a positive polymerase chain reaction (PCR) test. The severity was divided into mild, moderate, severe, and critical according to the guidelines of the United States National Institutes of Health (NIH). Results: A total of 140 individuals (37 males, 103 females; mean age 56.1 ± 11.3 years) with rheumatic disease diagnosed with COVID-19 infection were enrolled in the study. AIRDs included rheumatoid arthritis (RA) (n = 63, 45%), ankylosing spondylitis (AS) (n = 35, 25%), systemic lupus erythematosus (SLE) (n = 26, 8.6%), and systemic sclerosis (SSc) (n = 16, 11.4%). The AIRDs group had more SARS-CoV-2-related dyspnea (38.6%), arthralgia (45.7%), and depression (27.1%) than the control group (p = 0.004). The rate of lung infiltration on radiographic examination was higher in 58 (41.4%, p = 0.005) patients with rheumatic diseases than in those without them. Severe SARS-CoV-2 infection was more common in the AIRDs group than in the control group (22% vs. 12%; p = 0.043). Conclusions: Patients with AIRDs experienced more symptoms of arthralgia, depression, and dyspnea. There was a trend towards an increased severity of the disease in patients with AIRDs. Patients with arterial hypertension, diabetes, chronic lung, and kidney disease, treated with corticosteroids, had a longer duration, and high activity of autoimmune disease had an increased risk of severe COVID-19.

Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.

Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD). Sera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Linköping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-α was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD. In total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-α reported mild sicca symptoms and were diagnosed with Sjögren's disease after clinical evaluation. A considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-α levels identified the small proportion of individuals with SARD in the study population.

Long-Term Mortality Following SARS-CoV-2 Infection in Rural Versus Urban Dwellers With Autoimmune or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From the National COVID Cohort Collaborative.

Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two-year all-cause mortality. Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for two-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher two-year all-cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19-1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two-year post-COVID-19 mortality, whereas risk with nonbiologic or biologic disease-modifying antirheumatic drugs was lower. Rural residence in people with AIRD was independently associated with higher two-year post-COVID-19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among high-risk rural residents.

Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors.

Hepatitis B reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. We conducted a SLR (PubMed, Scopus and EMBASE) and metanalysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. Overall, our study revealed a low HBVr risk of < 6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14,4% vs 5.1%, respectively p< 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis the respective percentage was 4.7%. Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.

Clinical outcomes and risk factors in patients with COVID-19 and autoimmune rheumatic diseases: insights from a major Australian hospital study.

Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID-19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccine status, were associated with more severe forms of COVID-19 infection. Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID-19 infection were analysed using a binary regression model and a multinomial regression model. The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35-25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21-23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63-19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05-0.69) and three and four doses (OR = 0.09; 95% CI = 0.02-0.35) were all statistically significant factors related to changes in the severity level of COVID-19. Severity of COVID-19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID-19 severity.

Breakthrough SARS-CoV-2 infection in fully vaccinated patients with systemic lupus erythematosus: results from the COVID-19 Vaccination in Autoimmune Disease (COVAD) study

ObjectiveTo determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).MethodsThe study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models.ResultsA total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89–6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04–5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively.ConclusionCOVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals.

Central Nervous System Involvement in Systemic Autoimmune Rheumatic Diseases-Diagnosis and Treatment.

Central nervous system (CNS) involvement in autoimmune rheumatic diseases represents a significant challenge for clinicians across all specialties. While most reviews on the subject focus on neurological manifestations within a specific rheumatic disease, few descriptions shift from neurological clinical syndromes to achieve rheumatological diagnoses. This narrative review aims to synthesize current knowledge on the diagnosis and management of CNS manifestations occurring in the most prevalent rheumatic conditions in adults. We searched the MEDLINE database using the terms "central nervous system", "rheumatic diseases", "systemic lupus erythematosus", "rheumatoid arthritis", "Sjögren syndrome", and "vasculitis". The search strategy included review articles from 2019 to 2024, published in English, Spanish, or Portuguese. We explored the pathophysiological mechanisms linking autoimmunity to CNS pathology, emphasizing the role of syndromic reasoning, autoantibody profiles, and imaging modalities as tools for diagnosis and determination of inflammatory activity. The review also discusses differential diagnoses through a stepwise approach to neurological syndromes, summarized in diagnostic flowcharts, and presents updated treatment options. Although our approach is primarily semiology-based, the complexity of the subject invites future endeavors involving new technologies, such as functional MRI, MR spectroscopy, and nuclear medicine.

Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases.

Multiple factors contribute to the development of connective tissue diseases (CTD), often alongside a range of interstitial lung diseases (ILD), including Sjögren's syndrome-associated ILD, systemic sclerosis-associated ILD, systemic lupus erythematosus-associated ILD, idiopathic inflammatory myositis-associated ILD. TRIM21(or Ro52), an E3 ubiquitin ligase, plays a vital role in managing innate and adaptive immunity, and maintaining cellular homeostasis, and is a focal target for autoantibodies in various rheumatic autoimmune diseases. However, the effectiveness of anti-TRIM21 antibodies in diagnosing CTD remains a matter of debate because of their non-specific nature. Recent studies indicate that TRIM21 and its autoantibody are involved in the pathogenesis of CTD-ILD and play an important role in diagnosis and prognosis. In this review, we focus on the contribution of TRIM21 in the pathogenesis of CTD-ILD, as well as the potential diagnostic value of its autoantibodies in different types of CTD-ILD for disease progression and potential as a novel therapeutic target.

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases.

The gut microbiota is a complex ecosystem of microorganisms residing in the human gastrointestinal tract, playing a crucial role in various biological processes and overall health maintenance. Dysbiosis, an imbalance in the composition and function of the gut microbiota, is linked to systemic autoimmune diseases (SAD). Short-chain fatty acids (SCFAs), especially butyrate, produced by the gut microbiota through the fermentation of dietary fibers, play a significant role in immunomodulation and maintaining intestinal homeostasis. Butyrate is essential for colonocyte energy, anti-inflammatory responses, and maintaining intestinal barrier integrity. Studies show reduced butyrate-producing bacteria in SAD patients, suggesting that increasing butyrate levels could have therapeutic benefits. Butyrate's anti-inflammatory effects and its potential therapeutic role have been studied in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, systemic sclerosis, and Behçet's disease. Despite promising in vitro and animal model results, human studies are limited, and the optimal strategies for modulating dysbiosis in SADs remain elusive. This review explores the current evidence on the immunoregulatory role of butyrate and its potential therapeutic effects in SAD.

Cardiovascular Events During Pregnancy: Implications for Adverse Pregnancy Outcomes in Individuals With Autoimmune and Rheumatic Diseases.

This study examined maternal cardiovascular (CV) events relative to adverse pregnancy outcomes among individuals with autoimmune rheumatic diseases (ARDs), primary antiphospholipid syndrome (APS), and those with neither. Using a California population-based birth cohort (2005-2020), we identified those with CV events (CVEs), ARDs, and APS through International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes in maternal discharge records. Selected adverse pregnancy outcomes identified from birth certificates were preterm birth (PTB; < 37 weeks' gestation), small-for-gestational-age infants (SGA; birth weight < 10th percentile for age and sex), and a composite of either outcome. Adjusted risk ratios (aRRs) for adverse outcomes and their 95% CIs were calculated. CVEs occurred more frequently in individuals with ARDs (265 of 19,340 [1.4%]) and primary APS (428 of 7758 [5.5%]) than those without (17,130 of 7,004,334 [0.3%]). The presence vs absence of CVEs was associated with a greater incidence of adverse outcomes in ARD (53.2% vs 26.6%), APS (30.6% vs 20.7%), and non-ARD/APS pregnancies (28.2% vs 15.2%). CVEs were associated with increased risks of SGA in all groups (aRRs 1.2-1.5) and PTB in ARD (aRR 1.6, 95% CI 1.3-2.0) and non-ARD/APS (aRR 1.7, 95% CI 1.7-1.8) pregnancies. CVEs were associated with modestly increased risks (20-70%) for PTB, SGA, or both across the groups. Notably, > 50% of ARD pregnancies with CVEs experienced adverse pregnancy outcomes. Given that ARD and APS pregnancies have higher (although still low) rates of CVEs and have higher baseline risks of adverse pregnancy outcomes than the general population, the additional burden conferred by CVEs is clinically important.

COVID-19 and autoimmune rheumatic disease: behavioural changes adopted by patients amid the pandemic.

Amid concerns about severe COVID-19 in patients with autoimmune rheumatic disease (AIRD) during the outbreak, it is crucial to explore behavioural changes, whether healthy or unhealthy, arising from this patient population in response to the changing healthcare environment. To investigate COVID-19-driven behavioural changes in patients with AIRD. This observational study invited patients who attended the rheumatology clinic of the Korle Bu Teaching Hospital from 1 August 2020 to 1 July 2021, to respond to a survey questionnaire distributed on the patient's WhatsApp platform. Variables observed were changes in patient behaviour and decision-making related to medication, healthcare service utilisation and clinical advice. Results for 233 patients were analysed in the study, the majority (89.7%) of whom were women. The most significant behavioural changes were a reduction in hydroxychloroquine (HCQ) dosage, adoption of telemedicine for clinical consultation and keen adherence to protective/preventive health measures. Patients also expressed anxiety regarding the risk of contracting COVID-19 (52.5%), infecting their families (66.5%) and losing income (50.2%) due to the pandemic. Women and students were more likely to engage in self-isolation/shielding behaviour. Employed participants practised social distancing more, reduced HCQ dosage and had more fear of losing income. Having mixed connective tissue disease is associated with being anxious about the risk of COVID-19 infection. The COVID-19 pandemic has resulted in behaviour changes among patients with AIRD. Despite the perceived risk, most of these patients continue to adhere to their prescribed medication regimens, especially maintaining the dosage of traditional immunosuppressive agents.

Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC.

Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.

Detection of systemic autoimmune diseases in an ongoing assessment program for hand arthralgias. A comparative analysis with inflammatory and non-inflammatory arthropathies.

Arthralgias are prevalent in systemic autoimmune rheumatic diseases (SARD), emphasizing the need for early recognition. This study aimed to estimate SARD frequency and compare clinical, laboratory, and imaging findings among SARD, non-inflammatory arthralgia (NIA), and RA in patients with hand arthralgias. A prospective evaluation program included individuals aged ≥18 with hand arthralgias. Baseline assessments covered clinical, laboratory, ultrasound, and radiography. Follow-up diagnoses categorized patients into SARD, NIA, and RA groups. Comparison between groups was performed using parametric and non-parametric tests. Two multivariate logistic regression analyzes were performed using the final diagnosis of SARD as the dependent variable (NIA and RA). ROC curves were calculated in those variables that presented an independent association in the multivariate analysis. Among 1053 patients, 9.6% were SARD (SLE 47%). Comparing SARD with NIA revealed higher CRP levels, power Doppler, less rhizarthrosis in ultrasound, and more ANA positivity in SARD patients. Distinct differences were observed between SARD and RA patients in terms of pain levels, swollen joints, metacarpophalangeal involvement and morning symptoms. Diagnostic markers demonstrated specific sensitivities and specificities: ANA for SARD versus NIA (82%, 34%), US not finding rhizarthrosis for SARD versus NIA (66%, 85%), CRP (cut-off >2.5 mg/L) sensitivity 52%, specificity 60%, AUC 0.62, RA antibodies (RF, 11 IU/mL) sensitivity 76%, specificity 74%, AUC 0.8, ACPA (1.25) sensitivity 50%, specificity 98%, AUC 0.7, ANA+ sensitivity 95%, specificity 32%, AUC 0.7, and US absence of synovitis sensitivity 82%, specificity 34%, AUC 0.75. This study highlights distinct clinical, laboratory, and imaging features differentiating SARD-related hand arthralgia from non-SARD hand arthralgia and RA.

Autoimmune dysphagia.

Dysphagia is a complication of several autoimmune rheumatic diseases and otorhinolaryngologists are likely to be involved in the assessment and management of patients with such conditions. This review provides an update on rheumatic diseases that may cause swallowing impairment, with particular focus on the epidemiology, pathophysiology and management of dysphagia in these conditions. Dysphagia is a common complication of the following rheumatic diseases: idiopathic inflammatory myopathies, systemic sclerosis, Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. It may also be a complication of rarer autoimmune conditions such as Bechet's syndrome, sarcoidosis and granulomatosis with polyangiitis. All three stages of swallowing (oral, pharyngeal and oesophageal) may be impaired in these conditions. Both medical therapy and surgical intervention play an important role in the management of autoimmune dysphagia. The investigation and management of autoimmune dysphagia requires close collaboration between rheumatologists and otorhinolaryngologists. There is a need for further research to establish standardised guidelines on the assessment and management of autoimmune dysphagia.

Serological response after COVID-19 infection compared to vaccination against COVID-19 in children with autoimmune rheumatic diseases

BackgroundPaediatric patients with autoimmune rheumatic diseases (pARD) have a dysregulated immune system, so infections present a major threat to them. To prevent severe COVID-19 infections we aimed to vaccinate them as soon as possible. Studies have shown that the BNT162b2 vaccine is safe, effective, and immunogenic, however, in a short observation period, only.MethodsThe main objective was to compare the serological response between three groups of pARD: after SARS-CoV-2 infection, after vaccination against COVID-19 with two doses of the BNT162b2 vaccine, and after experiencing both events. Data on demographics, diagnosis, therapy, and serology (anti-SARS-CoV-2 IgG/IgA) were collected from March 2020 to April 2022. For statistical analysis ANOVA, Mann-Whitney U test, Chi-square test and Fisher’s exact test were applied. To compare adverse events (AE) after vaccination we included a control group of healthy adolescents.ResultsWe collected data from 115 pARD; from 92 after infection and 47 after vaccination. Twenty-four were included in both groups. Serological data were available for 47 pARD after infection, 25 after vaccination, and 21 after both events. Serological response was better after vaccination and after both events compared to after infection only. No effect of medication on the antibody levels was noted. The safety profile of the vaccine was good. Systemic AE after the first dose of the vaccine were more common in healthy adolescents compared to pARD. In the observation period of 41.3 weeks, 60% of vaccinated pARD did not experience a symptomatic COVID-19 infection.ConclusionsIgG and IgA anti-SARS-CoV-2 levels were higher after vaccination and after both events compared to after infection only. Six months after vaccination we observed an increase in antibody levels, suggesting that pARD had been exposed to SARS-CoV-2 but remained asymptomatic.Trial registrationThe study was approved by the Medical Ethics Committee of the Republic of Slovenia (document number: 0120–485/2021/6).

Vitamin D and Muscle Status in Inflammatory and Autoimmune Rheumatic Diseases: An Update.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020-2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.