Rheumatoid Factor Research Articles

The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial.

Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis. This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS). Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre≥1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of≥10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P=0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P=0.002]. IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA. ClinicalTrials.gov identifier, NCT01366209.

Prevalence of Subclinical Peripheral Neuropathy in Patients With Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

Background Autoimmune connective tissue disorders (AICTDs) are a group of chronic inflammatory diseases characterized by immune responses targeting the body's own tissues. Peripheral neuropathy, which can be symmetrical or asymmetrical, is a common complication in AICTD patients. Early detection of subclinical peripheral neuropathy remains challenging, as nerve conduction studies are not routinely performed. This study aimed to determine the prevalence of subclinical peripheral neuropathy among patients with AICTD and to assess its association with potential predictor variables, including laboratory parameters and autoimmune markers. Materials and methods This observational cross-sectional study included 100 patients undergoing treatment for AICTDs for over three years, conducted over 15 months. Ethical approval and informed consent were obtained before detecting subclinical peripheral neuropathy through nerve conduction studies on bilateral ulnar, radial, sural, peroneal, and tibial nerves at a tertiary-level medical college hospital. Inclusion criteria encompassed patients treated at the tertiary hospital, not on immunosuppressants other than steroids, with at least three years of treatment, while exclusions were made for established peripheral neuropathy and other specified conditions. Descriptive statistics, Chi-square/Fisher's exact tests, independent samples t-tests, and logistic regression were used for data analysis at a 0.05 significance level, with IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, NY, USA). Results Subclinical peripheral neuropathy was present in 18% (n = 18) of the study participants, while 82% (n = 82) did not exhibit neuropathy. Patients with subclinical neuropathy had a significantly higher mean age (49.66 ± 4.77 years) compared to those without neuropathy (46.02 ± 12.7 years, p = 0.047). The majority of the study population was female, 79 (79%), and there was no significant gender difference between the groups (p = 0.513). There was no significant association between inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and neuropathy. However, patients with subclinical neuropathy were more likely to test positive for rheumatoid factor (RF) (8 (66.7%) vs. 71 (58.5%), p = 0.011) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies (11 (78.5%) vs. 32 (47%), p = 0.032). Steroid use did not significantly affect the presence of neuropathy (p = 0.769). Conclusion The study found a high prevalence of subclinical peripheral neuropathy in AICTD patients, detectable only by nerve conduction studies. RF and Anti-CCP antibodies were associated with subclinical neuropathy, suggesting these markers could guide early detection, and inform treatment intensification to reduce neuropathy prevalence among AICTD patients.

“Mechanic’s Hand” with Polyarthralgia and Transient Autoimmune Features after COVID Vaccination

Abstract Autoimmune diseases are now well reported with COVID vaccination. Rheumatological, neurological, cardiac, and hematological adverse events are observed globally. Dermatological adverse events are reported in a few cases but dermatological with rheumatological manifestation with reversible autoimmune phenomenon after COVID vaccination is not reported commonly in literature. “Mechanic’s hands” is blackish discoloration of palmar aspects of both hands and knuckles commonly reported in rheumatological autoimmune condition such as dermatomyositis. In this case report, a 28-year-old male presented with polyarthralgia with myalgia and fatigability after 1 month of COVID vaccination. His joint pain symptoms worsened over 4 weeks and developed blackish pigmentation of both hands predominantly involving palms to present as mechanic’s hands. Vasculitis workup was inconclusive and rheumatologic workup documented raised antinuclear antibody titers and rheumatoid factor. We have started him on steroid and hydroxychloroquine and observed satisfactory clinical response with near complete resolution of “mechanic’s hands” in 24 weeks. Mechanic’s hands with rheumatological syndrome which is a rare vaccine-related adverse event, reversible, and easily treatable with routinely available medicines, and importantly it is having excellent prognosis. Mechanic’s hand is first time reported in medical literature after COVID vaccination. Minimal systemic adverse events are known to occur with all viral vector vaccines, but its occurrence is rare and it should not impact on routine vaccinations, as vaccination is a key step in this pandemic to protect humankind.

Low Haemoglobin is Inversely Associated with Disease Activity in Rheumatoid Arthritis: A Cross-Sectional Study from a Tertiary Care Hospital.

Extra-articular manifestations especially haematological abnormalities are common in Rheumatoid arthritis (RA). The aim is to study the haematological parameters and its correlation with disease severity and gender. A cross-sectional study was conducted at a tertiary centre among 50 RA patients who attended the Rheumatology or General Medicine OPD from January 2020 to June 2021. The number of swollen joints, tender joints, the patient's global assessment, rheumatoid factor, and complete blood counts were recorded. Disease Activity Score (DAS-28) was calculated from these variables and data was analysed using SPSS version 29 with p<0.05 considered as statistically significant. Of the study subjects, forty (80%) were females; thirty (60%) belonged to the age group 41-50 years. Median age was 42.4(18, 50) years. 79 % (19 out of 24) of subjects with normal haemoglobin had moderate disease activity on DAS 28 score and 50% (13/26) of participants with low haemoglobin levels had high disease activity. Simple linear regression analysis showed low haemoglobin is inversely associated with DAS 28 score (R2 = 0.407, F= 32.888, p < 0.001). Compared to females, males had a higher haemoglobin level which was statistically significant. Female patients had statistically significant higher DAS 28 scores than males (p = 0.016). Low haemoglobin levels are associated with high disease activity in RA patients and males had less severe disease than females.

Potential of salivary biomarkers for diagnosing and prognosing rheumatoid arthritis: A systematic review and meta-analysis: Salivary biomarkers in Rheumatoid Arthritis patients – A systematic review with Meta-analysis

BackgroundRheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder. Blood biomarkers, like rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), lack the sensitivity and specificity for early diagnosis, delaying treatment. This review while highlighting the need for new diagnostic tools, emphasizes the promising avenue of saliva for developing RA biomarkers. ObjectiveThis systematic review and meta-analysis assess the effectiveness of salivary biomarkers in the diagnosis and prognosis of RA, examining current evidence and proposing avenues for future research. MethodologyA literature review following PRISMA 2021 guidelines was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies from the past five years on salivary biomarkers in RA patients compared to healthy controls. ResultThe review focused on original research articles, and meta-analysis was performed on studies reporting standard deviation values for inflammatory markers such as IL-6, IL-8, MMP-8, and TNF-alpha. The meta-analysis included eleven studies with 394 RA patients and 255 healthy controls, evaluating IL-8, IL-6, MMP-8, and TNF-α as RA biomarkers. IL-8 showed a mean difference of 7.32 (CI: -5.48 to 20.13), not statistically significant, favouring controls. IL-6 had a CI of -0.09 (CI: -2.20 to 2.02) with high heterogeneity (I² = 98%), suggesting its potential as a diagnostic and prognostic biomarker. TNF-α and MMP-8 showed no significant differences (CIs: 4.54 and 2.71, respectively). ConclusionThis systematic review and meta-analysis emphasize saliva's potential in identifying RA biomarkers, especially IL-6, which is associated with the disease's pathogenesis. However, significant evidence heterogeneity necessitates larger, multicentric studies for validation.

Predictors of Drug Retention and Survival Rate of bDMARDs in Rheumatoid Arthritis: A Four-Year Real-Life Tunisian Experience.

This study aims to investigate the efficacy and tolerance of biologic disease-modifying anti-rheumatic drug (bDMARDs) in the current management of rheumatoid arthritis (RA) by identifying the retention time and survival rate of bDMARDs. We conducted a retrospective cohort study including Tunisian patients initiating bDMARD treatment between 2016 and 2018 whose data were collected from the National Health Insurance Fund (NHIF). The NHIF is the national office which organises and centralises patients under bDMARDs from all over the country. Retention and survival rate of bDMARDs at 48 months were analysed using Kaplan-Meier survival curves and compared using the log-rank test. Survival factor analysis was performed using Cox regression. Three hundred seventy-four patients, aged 55.5±12.5years [20-90], (87.2%women), were included. The mean duration of RA was 11.7±6.7 years [2-41]. The mean disease activity score (DAS)28 at initiation of the first bDMARD was 6.01±0.89 [5.37-6.5]. This first bDMARD induced low disease activity (LDA) in 55% of cases. Remission was observed in 28% of patients. The highest LDA and remission rates were observed with Tocilizumab (70.8% and 33.3% of cases, respectively). LDA and remission were achieved within a mean of 45 weeks [26-88] and 72 weeks [31-117] respectively. The 48-month first-line survival rate was 55.9%. Retention time was 41.7 months, 95%CI [39.47-43.91]. Presence of rheumatoid factors, co-prescription of methotrexate, and good initial therapeutic response were factors influencing better survival of bDMARDs (p<0.01). Glucocorticoid use predicted poorer survival (p<10-3). The first bDMARD was interrupted in 39% of cases. Ineffectiveness was the most common cause of treatment cessation (52.7%). This real-life study of the Tunisian population allowed us to establish the factors that can influence the survival and retention rates of bDMARDs.

Oral Complications Due to Medication in Stevens-Johnson Syndrome Patient with Systemic Involvement

Background: Stevens-Johnson Syndrome (SJS) is a drug-induced hypersensitivity reaction involving mucocutaneous with various trigger factors including drugs and herpes simplex virus. Objective: This case report aimed to discuss oral complications due to medication in SJS patients with systemic disease involvement. Case: A 51-year-old man was referred to the Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, at Hasan Sadikin Hospital from the dermatology and venereology department complaining of pain in the oral cavity, especially when eating and drinking two months before, with a history of phenytoin, salbutamol and theophylline therapy. Extraoral examination showed erosive lesions and tended to bleed serosanguinolenta crusts on the lips. Intraoral there were erosive lesions and white plaque on the tongue, buccal mucosa, labial mucosa, and palate, as well as dental caries and calculus. Blood examination showed low hemoglobin, hematocrit, erythrocytes, lymphocytes, monocytes, SGOT, and sodium levels, while HbA1c, random, fasting, and 2 HPP glucose levels were high. Reactive Anti-HSV-1 IgG and rheumatoid factor. KOH examination showed positive spores, hyphae, pseudohypha, and budding cells. The diagnosis was SJS-associated oral lesions with HSV-1 virus infection, oral candidiasis accompanied with diabetes mellitus. For diabetes mellitus treatment, he was referred to the internal medicine department. Case Management: The therapy was 0.9% NaCl for lip compress, acyclovir tablet, nystatin oral suspension, chlorhexidine digluconate 0,12% mouthwash, folic acid, and vitamin B12. Oral lesions were improved significantly after diabetes mellitus was treated. Conclusion: The SJS patient was susceptible to complications in the oral cavity, especially fungal and viral infections due to the received medication.

The Effectiveness and Safety of Wu Tou Decoction on Rheumatoid Arthritis-A Systematic Review and Meta-Analysis.

Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the joints and requires various treatments, including medication, injection, and physiotherapy. Wu tou decoction (WTD) is a traditional Chinese medicine prescribed for RA, with several articles documenting its effectiveness in RA treatment. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of WTD for RA. We searched for randomized controlled trials (RCTs) comparing WTD with conventional treatments (including medication, injection, and physiotherapy) from its inception to May 2024. Primary outcomes were disease activity scores, including effective rate, tender joint count, and morning stiffness. Secondary outcomes comprised blood test results (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. Nineteen RCTs involving 1794 patients were included. Statistically, WTD demonstrated better improvement than conventional treatments (18 medications and 1 injection) across the effective rate, joint scale, and blood tests, regardless of the treatment type (monotherapy or combination therapy). Adverse events were reported in 11 studies, with no statistical differences observed between them. The numerical results showed that WTD may offer potential benefits for managing RA. However, the significant discrepancy between clinical practice and the low quality of the RCTs remains a limitation. Therefore, further well-designed studies with larger patient cohorts are needed to draw definitive conclusions.

Disease Damage in Juvenile Idiopathic Arthritis.

To estimate the prevalence and predictors of disease-related damage in children with juvenile idiopathic arthritis (JIA) in a resource-limited setting. A single-centre study was conducted from January 2021 - December 2022. Children (≤ 18 y) diagnosed with JIA as per International League of Associations for Rheumatology (ILAR) criteria, with a disease duration of more than one year, were enrolled for this study. The articular and extra-articular damage was assessed using the juvenile arthritis damage index (JADI) and modified JADI scores. Disease activity and disabilities were evaluated using the clinical juvenile arthritis disease activity score (cJADAS) and Childhood Health Assessment Questionnaire (CHAQ). One hundred and five children [44% (n = 42) boys] with JIA were enrolled in the study. The mean (SD) age of children at enrolment was 158 (46.2) mo. The median (IQR) disease duration was 48 (36-72) mo. Articular damage (JADI score ≥ 1) was present in 48.6%, and extra-articular damage (JADI-E ≥ 1) was observed in 21.9% of children. Half of the children (n = 22) with enthesitis-related arthritis (ERA) had joint damage (modified JADI score ≥ 1). Four children had ocular damage due to uveitis. Among the factors associated with articular damage, the odds of articular damage were high in those with positive rheumatoid factor (RF) and/ or anti-cyclic citrullinated peptides (CCPs) [OR: 4.4, 95% CI (1.00-19.60)]. 48.6% of children with JIA had articular damage, while 21.9% of the children had extra-articular damage. Children with RF and/ or anti-CCP positivity are associated with higher odds of joint damage.

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

USE OF THE DISEASE-MODIFYING DRUG LEFLUNOMIDE IN PATIENTS WITH RHEUMATOID ARTHRITIS

This paper is dedicated to an urgent problem of modern medicine, namely the treatment of rheumatoid arthritis. According to the literature, the activation and proliferation of the T-cell and macrophage pool with the involvement of synoviocytes/chondrocytes plays an important role in the pathoge. It is known that the mechanism of action of the active metabolite leflunomide (A771726) blocks dihydroorotate dehydrogenase, which in turn inhibits pyrimidine synthesis in rapidly dividing cells (activated T-lymphocytes, macrophages). As a result, leflunomide blocks the main link in the pathogenetic mechanism of rheumatoid arthritis development and progression.nesis of rheumatoid arthritis, which in turn leads to the destruction of articular cartilage. The study involved 52 patients with rheumatoid arthritis. This group of patients was represented predominantly by women (46 patients); the majority were seropositive for rheumatoid factor (RF) – (42 patients). The drug was prescribed according to the standard scheme: 100 mg/day for the first 3 days, then 20 mg/day. The dose was temporarily reduced in some patients to 10 mg/day in case of intolerance reactions. The effectiveness of leflunomide was evaluated in relation to the effect on indicators of RA activity and progression. In 30% of patients, the duration of rheumatoid arthritis at the time of leflunomide prescription was less than 3 years, in 46% – 4–10 years, and in 24% – more than ten years. Radiological stages III–IV were recorded in 70% of patients. With the exception of 2 patients with rheumatoid arthritis activity of grade II–III, and according to the criteria of the European Anti-Rheumatic League using the Disease activity score (DAS), all patients had moderate to high RA activity. In 35 patients (70%), arthritic manifestations were detected before the start of therapy. The rapid effect of action of Leflunomide is certain with the reliable decline of indexes of arthritis syndrome and laboratory indexes of activity of inflammation in 1 month of treatment.

Evaluation of Anti-arthritic Activity of hydro-alcoholic Root Extract of Moringa concanensis in complete Freund’s Adjuvant-induced Arthritic Rats

Background: Arthritis, a debilitating inflammatory disorder, has been a target for numerous therapeutic interventions. Natural plant extracts, especially those rich in phytochemicals like terpenoids, have demonstrated potential as alternative remedies. In this context, Moringa concanensis, a traditionally known medicinal plant, needs further elucidation regarding its anti-arthritic efficacy. Objective: This study aimed to investigate the anti-arthritic potential of the hydro-alcoholic root extract of Moringa concanensis in a Complete Freund’s Adjuvant (CFA)-induced arthritis rat model. Methods: An initial phytochemical screening and GC-MS analysis were executed on the hydro-alcoholic root extract of Moringa concanensis. Arthritis was subsequently induced in rats using CFA. Comprehensive assessments were made on various parameters such as body weight, paw volume, joint diameter, serum rheumatoid factor, serum C-reactive protein, ALP, ALT, total protein, total cholesterol, and urea. Additionally, histopathological studies of the liver and ankle joints were carried out. For comparative efficacy, methotrexate was employed as a positive control. Results: Rats receiving the hydro-alcoholic extract at dosages of 200mg/kg (p.o) and 400mg/kg (p.o) exhibited a notable reduction in the physical and biochemical indicators of arthritis, in comparison to the untreated arthritic model. Histopathological observations further confirmed that the anti-arthritic effects of the hydro-alcoholic extract were on par with methotrexate. Conclusion: The hydro-alcoholic root extract of Moringa concanensis exhibited significant anti-arthritic activity, possibly attributed to its terpenoid content. The findings advocate for its potential application as a therapeutic agent in managing arthritis.

Topical issues of diagnosis and treatment of arthropathy associated with tonsillitis. (Literature review)

The problem of chronic tonsillitis (CT) and its complications remains one of the most urgent in modern otorhinolaryngology today. The high probability of developing associated diseases, such as rheumatic heart disease, nonspecific arthritis and glomerulonephritis, emphasizes the high importance of this nosological unit both in the practice of an otorhinolaryngologist and doctors of other specialties. Reactive arthritis occupies a special place among the complications of CT. Acute rheumatic fever (ARF) used to be the most common disease that was associated with streptococcal tonsillitis and was accompanied by reactive arthritis. Since 1959, patients with ARL have become less common, but cases of "aseptic" arthritis in patients with acute tonsillitis continued to be recorded, however, they did not have any other major criteria to confirm the diagnosis of ARL. This type of arthritis is called "Post-streptococcal reactive arthritis" (PSRA). Despite the fact that this disease has been known since the middle of the XIX century, there is very little information about its etiology and pathogenesis in the literature. The main symptoms of PSRA are usually similar to the articular syndrome in classical reactive arthritis and are clinically manifested by acute asymmetric non-migrating polyarthritis. Laboratory diagnosis of PSRA, in particular, the determination of titers of streptococcal antibodies plays an important role in confirming the diagnosis. A special place is occupied by the differential diagnosis of PSRA with rheumatic diseases (RH). The main diagnostic laboratory markers of RH are antinuclear antibodies, rheumatoid factor and antibodies to citrullinated proteins. Joint syndrome in PSRA is often stopped when nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed only in combination with antibacterial drugs. If arthritis does not respond to long-term treatment with antibiotics and NSAIDs, and especially if the patient has a history of recurrent CT, a planned tonsillectomy is required to prevent the development of a chronic form of tonsillitis-associated arthritis. The article presents an analytical review of domestic and foreign publications on the topic of CT complicated by reactive arthritis. The possible diagnostic methods necessary to confirm the diagnosis and exclude a wide range of arthritis of a different etiology are described.

Effect of Coping Strategies on Pain Intensity in Patients with Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease that imposes significant challenges globally. This research seeks to contribute valuable insights that can inform the development of targeted interventions, enhancing the quality of care for RA patients and potentially mitigating the broader societal burden associated with this chronic autoimmune condition. Objectives The main objective of the current study is to investigate the demographic, psychosocial, and clinical aspects of RA patients. Materials and Methods The study included 93 RA patients and examined their demographic characteristics, brief-Coping Orientation to Problems Experienced (COPE) strategies, the prevalence of depression and anxiety, pain experiences (Mankoski Pain Scale), and diagnostic markers (Disease Activity Score [DAS-28], Rheumatoid Factor [RF], Anti-Cyclic Citrullinated Peptide [ACCP]). Results The study revealed a bimodal age distribution, with a gender predominance aligning with established RA prevalence patterns. Patients exhibited a tendency toward adaptive coping strategies, notably religious coping, active coping, and positive reframing, with variability in maladaptive strategies. The prevalence of depression (14.0%) and anxiety (18.3%) among RA patients was consistent with documented mental health burdens. Pain experiences exhibited a heterogeneous spectrum, and diagnostic markers indicated elevated disease activity in a substantial proportion of patients, with varied distribution in RF and ACCP subcategories. Conclusion This study provides nuanced insights into RA, emphasizing the importance of personalized coping and pain management strategies. The prevalence of mental health challenges and the spectrum of pain experiences underscore the multidimensional nature of RA, informing holistic approaches to care for enhanced patient outcomes.

Identification and evolution of predictors of Sjögren's disease-associated mucosa-associated lymphoid tissue lymphoma development over time: a case-control study

Non-Hodgkin lymphomas have a substantial impact on individuals with Sjögren's disease. This study focuses on mucosal-associated lymphoid tissue (MALT) lymphomas, which constitute the majority of Sjögren's disease-associated non-Hodgkin lymphomas. We aimed to identify reliable lymphoma predictors in patients with Sjögren's disease and study their progression over time. In this case-control study, patients diagnosed with Sjögren's disease-associated MALT lymphoma, with a minimum of 3 years between Sjögren's disease diagnosis and MALT lymphoma diagnosis, were included from three centres specialising in Sjögren's disease (University of Athens, Athens, Greece; University of Pisa, Pisa, Italy; and University of Udine, Udine, Italy) and matched 1:1 with control participants with Sjögren's disease who did not have lymphoma according to age, sex, disease duration at last follow up, and treatment modality. Three harmonised datasets were constructed, curated, and analysed to identify MALT lymphoma predictors, representing three distinct timepoints in lymphomagenesis progression: V1 at Sjögren's disease diagnosis, V2 3-4 years before lymphoma diagnosis, and V3 0·5-1·5 years before lymphoma diagnosis. All recruited patients fulfilled the 2016 American College of Rheumatology-European League Against Rheumatism criteria for Sjögren's disease. The primary outcome was to identify MALT lymphoma predictors in Sjögren's disease, present at the timepoint of Sjögren's disease diagnosis and 3-4 years before the diagnosis of MALT lymphoma. A fast correlation-based feature selection and logistic regression model was used at V1 and V2 to identify MALT lymphoma predictors. The progression of potential predictors was studied across V1, V2, and V3. Histological parameters were not included in the analysis. An individual with lived experience of Sjögren's disease was involved in the study design. 80 patients with Sjögren's disease-associated MALT lymphoma were included in the V1 dataset, 68 in the V2 dataset, and 80 in the V3 dataset, and matched to control participants with Sjögren's disease who did not have lymphoma. In both groups, 72 (90%) of 80 participants were women and eight (10%) were men. The mean age at Sjögren's disease diagnosis was 48·6 years (SD 11·6) in the lymphoma group and 48·7 years (11·5) in the control group. All patients were White, with 88 (55%) of 160 individuals of Greek nationality and 72 (45%) of Italian nationality. At the V1 timepoint, rheumatoid factor was the only independent lymphoma predictor (odds ratio 3·33 [95% CI 1·96-5·64]). At the V2 timepoint, rheumatoid factor (3·66 [95% CI 2·08-6·42]) and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index ≥5 (3·88 [1·69-8·90]) were identified as independent lymphoma risk factors. The high disease activity during the transition from the V1 to V2 timepoint was attributed to specific B-cell-derived manifestations, including cryoglobulinaemia and glandular, cutaneous, and hematological manifestations. Following up patients with high-risk of Sjögren's disease-associated MALT lymphoma based on the temporal progression of predictors presents an opportunity for early diagnosis and potential therapeutic interventions. Rheumatoid factor was the earliest and most persistent independent predictor of lymphoma. Specific B-cell manifestations in combination with rheumatoid factor indicate a more advanced stage of the lymphomagenesis process. European Commission-Horizon 2020.

Interstitial Lung Disease Phenotypes and Predictive Risk Factors in Primary Sjögren's Syndrome.

Background/Objectives: The prevalence of Interstitial Lung Disease (ILD) and risk factors for its development in patients with primary Sjögren's syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-related ILD phenotypes. The aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To characterize different pSS-ILD phenotypes. Methods: Clinical, laboratory and imaging data of pSS patients attending our center from January 2019 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F = 6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases, ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients more often presented pSS-related hematologic abnormalities (p = 0.012), cutaneous involvement (p = 0.027), inflammatory arthralgias (p = 0.026), C4 hypocomplementemia (p = 0.012) and positive RF (p = 0.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p = 0.008) and presented more severe fibrosis on HRCT (p = 0.008). On the univariate analysis, higher ESSDAI (p = 0.011), Raynaud's phenomenon (p = 0.009), anti-Ro52 (p = 0.031), hypergammaglobulinemia (p = 0.011), Rheumatoid Factor (RF) (p = 0.038) and C4 hypocomplementemia (p = 0.044) at baseline were associated to ILD development during follow-up. On the multivariate analysis, the ESSDAI at baseline (p = 0.05) and Raynaud's phenomenon (p = 0.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a relatively common and clinically heterogenous pSS manifestation. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD.

Exploring pulmonary involvement in newly diagnosed rheumatoid arthritis, and psoriatic arthritis: a single center study

ObjectivesThis cross-sectional study aimed to determine the prevalence, manifestation, and risk factors of pulmonary involvement in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to evaluate the efficacy of various diagnostic tools in screening for pulmonary involvement.MethodsUntreated, newly diagnosed patients with RA and PsA underwent an extensive multimodal diagnostic approach including clinical and laboratory assessment, pulmonary function tests, and chest radiography.ResultsWe recruited 50 arthritis patients (26 RA, 24 PsA) and 26 control subjects. Respiratory symptoms were found in 36.0 % of arthritis patients and 11.5 % of controls (p = 0.031). Pathologically reduced breathing width (< 3.0 cm) was significantly more common in arthritis patients (64.0 %) than in controls (23.1 %) (p < 0.001). Pulmonary function test results did not differ significantly between groups. Chest radiography revealed pulmonary involvement in 37.0 % of arthritis patients, higher in RA (50.0 %) than in PsA (22.7 %). Notably, only 35.3 % of arthritis patients with radiographic pulmonary involvement were symptomatic, with 64.7 % being asymptomatic. Radiographic pulmonary involvement was associated with advanced age (p = 0.002) and increased rheumatoid factor levels (p = 0.024).ConclusionOur research underscores the significant prevalence of largely asymptomatic pulmonary involvement in newly diagnosed RA and PsA patients. These findings highlight the importance of an early, multidisciplinary screening approach, particularly for high-risk individuals. Further large-scale studies are needed to develop comprehensive screening protocols to improve early detection and treatment of pulmonary involvement in arthritis.

Integrating pretest probability for rheumatoid arthritis with likelihood ratios of RF and ACPA to improve clinical utility of rheumatoid arthritis autoantibody testing

Background and aimsRheumatoid arthritis (RA) manifests through various symptoms and systemic manifestations. Diagnosis involves serological markers like rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Past studies have shown the added value of likelihood ratios (LRs) in result interpretation. LRs can be combined with pretest probability to estimate posttest probability for RA. There is a lack of information on pretest probability. This study aimed to estimate pretest probabilities for RA. Materials and methodsThis retrospective study included 133 consecutive RA patients and 651 consecutive disease controls presenting at a rheumatology outpatient clinic. Disease characteristics, risk factors associated with RA and laboratory parameters were documented for calculating pretest probabilities and LRs. ResultsJoint involvement, erosions, morning stiffness, and positive CRP, ESR tests significantly correlated with RA. Based on these factors, probabilities for RA were estimated. Besides, LRs for RA were established for RF and ACPA and combinations thereof. LRs increased with antibody levels and were highest for double high positivity. Posttest probabilities were estimated based on pretest probability and LR. ConclusionBy utilizing pretest probabilities for RA and LRs for RF and ACPA, posttest probabilities were estimated. Such approach enhances diagnostic accuracy, offering laboratory professionals and clinicians insights in the value of serological testing during the diagnostic process.

The implication of anti-Ro60 with or without anti-Ro52 antibody in patients with systemic lupus erythematosus.

Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjogren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterised. Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity. Patient characteristics and disease outcomes, including High Disease Activity Status (HDAS) defined as an ever attainment of SLEDAI2K ≥10, adjusted mean SLEDAI (AMS), and time-adjusted mean clinical SLEDAI (excluding serologic activities) were compared using linear or logistic regressions. Furthermore, isolated or dual positivity of anti-Ro60 and anti-Ro52 were studied. Out of 409 patients, 47.2% were Ro+. Ro+ patients were predominantly Asian, had positive dsDNA and hypocomplementemia. They showed a higher likelihood of HDAS (OR 1.65, 95% CI 1.10-2.48, p= 0.015), AMS > 4 (OR 1.84, 1.18-2.88, p= 0.007), and more frequent use of glucocorticoids (OR 1.87, 1.16-3.03, p= 0.011) and immunosuppressants (OR 2.0, 1.26-3.17, p= 0.003). Additionally, 24.4% of Ro+ patients experienced sicca symptoms, and hypergammaglobulinemia was significantly more common. Multivariate analysis confirmed that Asian ethnicity, severe flares, AMS, hypocomplementemia, rheumatoid factor, proteinuria, leucopenia, and sicca symptoms were significantly linked to Ro positivity. Anti-Ro positivity is associated with higher disease activity and increased treatment needs. Ro positivity correlates with laboratory abnormalities such as hypocomplementemia and leucopenia. These findings highlight the importance of anti-Ro60/Ro52 testing in the clinical evaluation of SLE.

Prevalence and clinical significance of anti-SSA antibody in the Chinese health screening population.

Anti-SSA antibodies are non-organ-specific autoantibodies highly prevalent in various autoimmune diseases. This study primarily investigated the prevalence of anti-SSA antibodies in the health screening population. Additionally, we explored the clinical features of the anti-SSA antibody-positive population and evaluated the development of connective tissue diseases (CTD) over the years in individuals with anti-SSA antibodies for whom follow-up was available. 64045 individuals without a history of CTD from 2013 to 2022 who visited Peking Union Medical College Hospital for health screening were screened for autoimmune antibodies. 1.7% (1091/64045) of the Chinese health screening population were positive for anti-SSA antibodies, with a prevalence of 0.9% (290/33829) in men and 2.7% (801/30216) in women. Compared with matched autoantibody-negative controls, anti-SSA antibody-positive individuals had higher levels of serological abnormalities including erythrocyte sedimentation rate (ESR) [10 (6-15) mm/h vs. 7 (4-12) mm/h, p<0.0001], rheumatoid factor (RF) [7.15 (4.30-16.90) IU/ml vs. 5.00 (3.20-7.90) IU/ml, p<0.0001], and Immunoglobulin G [13.09 (11.20-15.45) g/L vs. 11.34 (9.85-13.18) g/L, p<0.0001], and lower levels of white blood cells (WBC) (5.49 ± 1.50 *109/L vs. 5.82 ± 1.49 *109/L, p<0.0001). Additionally, they had a higher proportion of coexisting thyroid autoantibodies, including anti-thyroid peroxidase antibodies (TPO-Ab) (17.1% vs. 11.3%, p<0.0001) and anti-thyroglobulin antibodies (Tg-Ab) (17.8% vs. 11.0%, p<0.0001). Among the 381 subjects who were anti-SSA positive and followed up for a median of 4.6 years, 146 (38.3%) individuals developed CTD, including 68 (17.8%) cases of primary Sjögren syndrome (pSS), 10 (2.6%) cases of rheumatoid arthritis (RA), 5 cases (1.3%) of systemic lupus erythematosus (SLE), and 59 (15.5%) cases of undifferentiated connective tissue disease (UCTD). 235 (61.7%) individuals did not develop CTD over a median time of 5.9 (2.9-8.1) years after the earliest autoantibody detection. Elevated ESR (>20mm/h), RF positivity (>20 IU/ml), and female gender were identified as independent risk factors for CTD among the anti-SSAantibody-positive individuals. Anti-SSA antibodies were found in 17 among approximately 1000 individuals without a history of autoimmune diseases. Anti-SSA antibody-positive individuals are advised to periodically monitor thyroid function. Elevated ESR (>20mm/h), female gender, and rheumatoid factor positivity may delineate a high-risk cohort for CTDs.