Criteria For Rheumatoid Arthritis Research Articles

A study of lipid profile peculiarities and atherogenic index of plasma in patients younger than fifty years of age with newly diagnosed rheumatoid arthritis

ABSTRACT Context: Cardiovascular disease (CVD) is an important cause of mortality in rheumatoid arthritis (RA). Aims: Evaluation of lipid profile and atherogenic index of plasma (AIP) in newly diagnosed DMARD naïve patients of RA younger than 50 years of age, and its comparison with age- and sex-matched healthy controls. Settings and Design: Cross-sectional comparative study. Methods and Material: 48 patients aged 18 to 50 years fulfilling the ACR/EULAR criteria for RA, not yet on DMARD or steroids and 51 healthy controls were included. Disease activity was assessed, and lipid profile was estimated: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and very low-density lipoprotein (VLDL). Atherogenic index of plasma (AIP) was calculated using a standard formula. Statistical Analysis Used: Independent sample t-tests were used to determine the statistical significance of mean values between the case and control groups. Pearson’s correlation test was used to correlate various components of the lipid profile and the atherogenic index with DAS28-ESR. Results: Significantly reduced levels of HDL (39.31 ± 6.52 mg/dl) were found in patients with RA as compared to the healthy controls. Serum TG was significantly higher in the cases (138.35 ± 39.23 mg/dl). TC level was significantly elevated in the cases. Mean atherogenic index in cases was significantly higher (0.17 + 0.14) in some cases. Only a weak correlation was found between lipid profile components and DAS28-ESR. Conclusions: Serum HDL level was significantly lower, and TC, TG levels and AIP were significantly higher in younger patients of early DMARD naïve RA pointing to a higher CV risk.

The effect of rituximab therapy and the risk of hypogammaglobulinamea on immunoglobulin levels in patients with rheumatoid arthritis

Background. Rituximab (RTX) is a biological monoclonal antibody targeting the CD20 antigen on B cells, effectively decreasing disease activity and progression in patients with rheumatoid arthritis (RA). RTX treatment can lead to a decline in plasma cells that produce immunoglobulin, potentially resulting in hypogammaglobulinemia (HGG). This study aims to assess the effect of RTX on immunoglobulin levels and determine the prevalence of HGG in RA patients after receiving different doses and cycles of RTX. Additionally, immunoglobulin levels were compared between patients treated with RTX and those treated with traditional disease-modifying antirheumatic drugs (DMARDs). We also sought to identify patient, disease, and therapy factors associated with HGG to evaluate the importance of monitoring immunoglobulin levels. Method. A single-center observational cross-sectional study was conducted at Baghdad Teaching Hospital between November 2023 and May 2024. Patients with RA were recruited and divided into two groups. The first group consisted of 45 RA patients receiving RTX, and the second group included 45 patients receiving DMARDs. All patients met the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 classification criteria for RA. Patients were excluded if they had received RTX for conditions other than RA or if they had been treated with RTX for less than six months. Quantitative IgG and IgA levels were measured via enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RTX on immunoglobulin levels and compare it with the effect of DMARDs. HGG was defined as an immunoglobulin level below two standard deviations from the mean of age-matched healthy controls. Results. Ninety patients were enrolled in the study, 45 of whom were treated with RTX. The mean number of RTX cycles was 3.67, ranging from 2 to 10 cycles. A significant decrease in immunoglobulin levels was observed post-RTX therapy, with 84.4% of patients exhibiting low IgG levels (<5 μg/ml), leading to HGG. The IgG levels in RTX-treated patients ranged from 4.3 to 22.0 μg/ml, with a mean of 7.28 ± 3.95 μg/ml. In contrast, patients treated with DMARDs maintained normal immunoglobulin levels similar to healthy individuals, with IgG levels ranging from 19.7 to 43.7 μg/ml. RTX also affected IgA levels, but to a lesser extent than IgG. Conclusion. Lower immunoglobulin levels following RTX therapy frequently result in HGG, emphasizing the importance of immunologic surveillance before and after treatment. DMARD therapy did not affect immunoglobulin levels, and concurrent use of DMARDs with RTX offered no protection against HGG. Additionally, HGG was not associated with an increased incidence of infections.

High-Titer Rheumatoid Factor is Associated with Worse Clinical Outcomes and Higher Needs for Advanced Therapies in Rheumatoid Arthritis Under Real-Life Conditions.

Rheumatoid factor (RF) plays an important role in rheumatoid arthritis (RA) pathophysiology, yet the differential effects of varying RF titers remain understudied. We evaluated associations between different RF titers and clinical outcomes in long-standing RA. This multicenter, cross-sectional study included adults meeting ACR/EULAR (2010) criteria for RA. Circulating RF titers and clinical-epidemiological characteristics were evaluated. Bivariate (Student's t and chi-squared tests) tests and multiple logistic and linear regression analyses were conducted. We included 1097 participants; 78.7% had positive RF, with high titers (≥ 3 × the upper limit of normality) in 56.2%. Negative vs. low-positive RF groups performed similarly concerning all clinical outcomes, being subsequently aggregated as "non-high" RF group. High RF titers (compared to "non-high") were associated with tobacco use (odds ratio, OR [95% confidence interval, CI]: 2.04 [1.35, 3.08]; p < 0.001), multiraciality (OR [95% CI] 1.31 [1.03, 1.67]; p = 0.028, compared to White race), and higher body mass index (mean difference [95% CI] 0.69 [0.05, 1.33] kg/m2; p = 0.033). In multivariate analyses, high-titer RF was independently associated with higher disease activity (Clinical Disease Activity Index, CDAI: β = 2.44 [0.89, 3.99], p = 0.002), worse functional capacity (Health Assessment Questionnaire Disability Index, HAQ-DI: β = 0.112 [0.018, 0.205], p = 0.020); extra-articular manifestations (OR 1.48 [1.09, 2.00], p = 0.011); increased corticosteroid (OR 1.53 [1.19, 1.96], p = 0.001) and biological disease-modifying antirheumatic drugs (bDMARD) use (OR 1.41 [1.08, 1.84], p = 0.011). High RF titers in long-standing RA were associated with worse disease activity, lower physical functionality, increased extra-articular manifestations, and higher usage of corticosteroids and bDMARDs. Comparing high vs. non-high RF titers (rather than positive vs. negative RF) seems more useful for evaluating the clinical effects of RF in RA. This approach should be considered in future studies of RF.

Immunomodulatory effects of novel nano micelle based curcumin in rheumatoid arthritis patients: A double blind randomized clinical trial.

Rheumatoid arthritis (RA) is a well-known systemic autoimmune inflammatory disease. This investigation aimed to assess the effects of Sina-curcumin, a novel nano micelle-based curcumin, on immune system responses of RA patients. This pilot study is a randomized double blinded, controlled trial. Patients who fulfilled the European League against Rheumatism-American College of Rheumatology (EULAR-ACR) criteria for RA were assigned to receive curcumin or placebo for 12 weeks. The outcomes of this study were comparison of changes in mean value of Disease Activity Score of 28 joints erythrocyte sedimentation rate (DAS28-ESR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), frequency of T helper 1 and T helper 2 cells population. From 150 RA patients who were assessed for eligibility, data from 30 patients (15 patients in each group) were analyzed. There was no significant difference between the two groups regarding age (P = 0.6441) and body mass index (BMI, P = 0.6016). Our measurement showed a statistically significant reduction in ESR (P < 0.0001), CRP (P < 0.0001) and a non-significant decrease in DAS28-ESR (P = 0.5125) in the curcumin group. Also, the Th1/Th2 ratio favorably decreased in the curcumin group. This finding was due to a significant increase in Th2 cells (P < 0.0001) and a nonsignificant decrease in Th1 cells (P = 0.1532). Our trial findings revealed the immunomodulatory effects of curcumin. It could be used and recommended as adjunctive treatment for RA patients.

Conventional Synthetic Disease-modifying Drugs Remain the Mainstay of Therapy for Rheumatoid Arthritis in India.

There are limited data on the real-world utilization of disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA). This was a cross-sectional study of a multicentric observational cohort of RA patients across rheumatology clinics at six centers across India. Patients who met the American College of Rheumatology (ACR) 2010 criteria for RA were included. The demographics, disease-related parameters, and current therapy in terms of DMARDs were analyzed using a structured paper or electronic case record form. This study included 4,061 patients with RA across six centers in India. A majority were female (female-to-male ratio, 6:1), and their mean [standard deviation (SD)] age at the time of enrollment was 51 (12.2) years. Rheumatoid factor and/or anti-CCP were positive in 79 and 77%, respectively. Data on DMARDs were available for 3,550 RA patients. Conventional synthetic DMARDs alone were being used in 3,289 (93%), targeted synthetic DMARDs in 203 (6%), and biological DMARDs in 67 (2%). A total of at least 18 separate types or combinations of DMARDs were being prescribed, with the most common being a combination of methotrexate and hydroxychloroquine (22%), methotrexate monotherapy (17%), and a combination of methotrexate and leflunomide (16%). Overall, the most common DMARD prescribed (as monotherapy or in combination) was methotrexate (86%), followed by hydroxychloroquine (52%) and leflunomide (37%). Cs-DMARDs remain the mainstay in the treatment of Indian patients with RA in this study, with the majority being treated with methotrexate alone or in combination with other DMARDs.

Incident rheumatoid arthritis in patients living in Turkey and in Denmark: a comparative clinical, genetic, and serological study

Objective The north–south gradient hypothesis proposes that individuals with rheumatoid arthritis (RA) residing in southern regions manifest a younger age of onset and milder disease compared to their northern counterparts. This study aimed to compare treatment-naïve, new-onset RA patients in Denmark and Turkey, examining demographic, clinical, laboratory, and genetic parameters. Method Prospective data collection was conducted, with all patients meeting the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Shared epitope (SE) allele carrier frequencies were examined for genetic comparisons between patients and normal controls. Results Out of 223 RA patients, 109 were Danish and 114 Turkish. Danish patients exhibited a median age at onset of 60 years, whereas Turkish patients were younger at 51 years (p = 0.0007). The Danish cohort displayed significantly more swollen and tender joints, resulting in higher Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP). Danish RA patients and controls possessed more RA risk-enhancing alleles (S2 + S3P) and fewer risk-protective (S1 + S3D) alleles than Turkish patients and controls. Conclusion This study substantiates the north–south gradient hypothesis, highlighting that new-onset RA patients in Denmark tend to experience an older age of onset and more severe disease activity than their Turkish counterparts. Variations in risk-enhancing alleles and fewer risk-protective alleles in Danish patients and controls are associated with these distinctions. Future research should investigate the genetic and environmental factors underlying these regional disparities, exploring their persistence in the long-term course of the disease through follow-up studies.

Evaluation of the clinical performance of anti-mutated citrullinated vimentin antibody and 14-3-3 eta testing in rheumatoid arthritis.

Early rheumatoid arthritis (RA) detection is crucial for improving patient prognosis. Anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) support RA diagnosis but are undetectable in ∼20 % of cases. Recently, antibodies against mutated citrullinated vimentin (anti-MCV) and detection of 14-3-3 eta have emerged with implications for preclinical RA diagnosis and monitoring treatment. The objective of this study was to assess the clinical performance of anti-MCV antibodies and 14-3-3 eta in RA and to compare it to current RA criteria anti-CCP and RF markers, individually and in combination. A retrospective chart review of 326 subjects submitted for RA serology testing identified 134 RA positive and 192 RA negative disease control individuals. Fifty healthy controls specimens were also included. Performance of anti-MCV and 14-3-3 eta, alone and combined with CCP3.1 and RF, was assessed. Anti-MCV had a sensitivity of 71 % and a specificity of 92 %. 14-3-3 eta had a sensitivity of 43 % and a specificity of 90 %. In comparison, CCP3.1 and RF displayed a sensitivity of 79 % and 84 % and a specificity of 92 % and 61 %, respectively. ROC curve analysis demonstrated CCP3.1 and anti-MCV had superior diagnostic performance compared to RF and 14-3-3 eta. In our cohort, anti-MCV and 14-3-3 eta failed to identify seronegative RA patients. Different combinations of double antibody positivity increased specificity at the cost of lost sensitivity. Individually, 14-3-3 eta, anti-MCV and CCP3.1 assays had≥90 % specificity in diagnosed RA patients, with better sensitivities for anti-MCV and CCP3.1 than 14-3-3 eta. Overall diagnostic performance of anti-MCV was similar to CCP3.1 and RF, all of which outperformed 14-3-3 eta in our cohort.

Routine radiographs of hands and feet do not have diagnostic or prognostic value in patients with clinically suspect arthralgia: a large longitudinal study

BackgroundConventional radiographs of hands and feet are used to depict structural damage in rheumatoid arthritis (RA). This is also commonly done in clinical practice in symptomatic patients at risk for...

Environmental pollution impact on the severity of some rheumatic diseases: a comparative analytical study on inflammatory and non-inflammatory samples

ObjectiveEnvironmental pollution of heavy metals is increasingly a problem and has become of great concern due to the adverse effects it causes worldwide. Heavy metal exposure has been implicated in health problems, including fibromyalgia and rheumatoid arthritis. We aim to evaluate the rule of chronic heavy metals toxicity on the induction of vitamin D3 (VD) deficiency and parathyroid hormone (PTH) disturbances in an inflammatory disease like rheumatoid arthritis (RA) and non-inflammatory disease like fibromyalgia syndrome (FMS).MethodsThis comparative analytical study was conducted on sixty adults (age ≥ 18 years). Participants were divided into three groups. Group I: twenty patients diagnosed with RA according to the specific ACR/EULAR criteria for RA. Group II: twenty patients diagnosed with FMS according to the specific 2010 (ACR) criteria for FMS. Group III: twenty healthy adults. All patients and controls were subjected to routine laboratory tests as well as the measurement of PTH, VD and estimation of serum levels of lead, cadmium, and chromium.ResultsVD was significantly inversely correlated to PTH, lead, cadmium, chromium, and activity scores in the RA and FMS groups. Lead, Cadmium and Chromium had a significant independent risk on the VD level in RA patients, while lead had a significant independent risk on the VD level in FMS patients.ConclusionHeavy metals may affect VD synthesis, leading to hypovitaminosis D and secondary hyperparathyroidism in RA and FMS patients. Heavy metals play a key role in the pathogenesis of RA, FMS, and their disease activity.

Systemic lupus erythematosus induced by anti-tumor necrosis factor α therapy in inflammatory rheumatic diseases: a case series.

This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

Socioeconomic status, reserve capacity, and depressive symptoms predict pain in Rheumatoid Arthritis: an examination of the reserve capacity model

BackgroundGuided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA).MethodsThe secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA).ResultsParticipants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain.ConclusionsThe findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA.Trial registrationclinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

Is the development of arrhythmia predictable in rheumatoid arthritis?

This study aimed to determine whether there is a difference in the electrocardiography (ECG) measurements of healthy controls and rheumatoid arthritis (RA) patients and to predict whether they can be used to determine the risk of arrhythmia in patients. The prospective study included 50 cardiac asymptomatic RA patients (38 males, 12 females; mean age: 46.8±9.1 years; range, 18 to 60 years) who met the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology RA criteria and 50 healthy volunteers (34 males, 16 females; mean age: 43.4±10.4 years; range, 18 to 60 years) as a control group between June 1, 2022, and August 31, 2022. Disease activity of the patients was calculated with the Disase Activity Score (DAS28). Heart rate, minimum and maximum QT intervals, QT dispersion, minimum and maximum P waves, P wave dispersion (Pd), minimum and maximum Tp-e intervals, Tp-e dispersion, minimum and maximum corrected QT (QTc) intervals, QTc dispersion, and the Tp-e/QTc ratio in ECGs were calculated. The mean disease duration of the RA group was 9.09±5.74 years. The mean C-reactive protein level was 9.83±8.29, the mean erythrocyte sedimentation rate was 26.12±16.28 mm/h, and the mean DAS28 was 3.03±0.37. There was a statistically significant increase in the maximum P wave, Pd, maximum QT, QT dispersion, maximum QTc, QTc dispersion, maximum Tp-e, Tp-e dispersion, and Tp-e/QTc dispersion parameters in the RA group compared to the control group, while there was a significant decrease in the minimum P wave, minimum QT, and minimum QTc parameters. In our study, the Pd, QTc dispersion, Tp-e dispersion, and Tp-e/QTc dispersion values of our patients, which indicate the risk of atrial and ventricular arrhythmia, were found to be significantly higher. This finding suggests that our patients had an increased risk of cardiac morbidity and mortality. Arrhythmias are the likely source of the increase in sudden cardiac death in RA, and these new indicators measured on ECG can be used as standardized cardiovascular morbidity and mortality indicators in the future.

Treatment modalities of marginal zone lymphoma and overall survival, haematological response, and underlying Sjögren's disease activity: a multicentre, retrospective, observational study

Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses. We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology-European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research. 106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70-37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21-0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14-0·94]). The were no differences in new Sjögren's disease systemic activity or overall survival according to combination therapy or monotherapy. A systemic treatment strategy for Sjögren's disease-associated lymphoma, rather than localised treatment or a watch and wait strategy, reduces the risk of new Sjögren's disease systemic activity and combination therapy is associated with decreased risk of lymphoma relapse. None.

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.

Questionnaire survey of the application of four objective indicators necessary for standardized diagnosis of Sjögren's syndrome

Objective: To investigate the current status and challenges of carrying out the four objective indicators which are necessary for the Sjögren's syndrome (SS) diagnosis in hospitals all over China. Methods: A questionnaire survey was conducted online by Questionstar from May to July 2023 among rheumatologists nationwide, to investigate whether unstimulated salivary flow (UWSF), Van Bijsterveld score (VBS), Schirmer test and labial gland focus score (FS) are carried out in their hospitals and the challenges that hinder their development. A cohort of patients with established SS was enrolled to verify the importance of the four objective indicators in diagnosing SS. Statistical analyses were performed using the chi-square test. Results: The questionnaire was completed by rheumatologists from 660 hospitals in 225 cities of 32 provinces, autonomous regions and municipalities all over China (one doctor from each hospital completed the questionnaire), of which 548 (83.0%) were tertiary care hospitals. The rate of carrying out the objective indicators in 660 hospitals was low: UWSF (290/660, 43.9%), FS (497/660, 75.3%) and VBS (393/660, 59.5%). The percentage of hospitals who consider it difficult to carry out UWSF, VBS, minor labial gland biopsy and Schirmer test was 92.6%(611/660), 69.4%(458/660), 59.8%(395/660) and 58.6%(387/660), respectively. All four objective indicators mentioned above could be carried out in only 139 (21.1%) hospitals. In 521 hospitals in which less than four objective indicators could be carried out, 23.2% (121/521) of rheumatologists selected clinical experience to diagnose SS. A total of 180 patients with SS diagnosed by perfecting all objective indices and meeting the 2016 the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were included, 173 females (96%), aged (46.6±13.6) years, with the missed diagnosis rate was 17.8% (32/180) assuming their labial FS was unavailable. In 166 patients with established SS who met the classic 2002 AECG criteria, 160 females (96%), aged (47.0±13.6) years, the missed diagnosis rate was 52.4% (87/166) assuming their labial FS was unavailable; or 10.8% (18/166) assuming their UWSF was unavailable. SS diagnosis couldn't be estimated according to 2002 AECG criteria, assuming both labial FS and UWSF were unavailable in 156 (94.0%) patients with positive anti-SSA/Ro; or assuming either labial FS or UWSF was unavailable in 10 (6.0%) patients with negative anti-SSA/Ro. Conclusion: The application rates of four objective indicators necessary for SS diagnosis are low, the rate of carrying out labial gland biopsy should be increased, and the labial FS reports and UWSF test should be standardized.

Turning the Tide against Herpes Zoster in Rheumatoid Arthritis Patients Treated with JAK Inhibitors.

Objectives: This study aimed to evaluate the incidence of Herpes Zoster (HZ) in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKi), and to predict potential risk factors for HZ development. Methods: We retrospectively analysed medical records from RA patients at our rheumatology unit who met the 2010 ACR/EULAR criteria for RA and were receiving JAKi. The incidence and course of HZ were assessed through chart review and supplementary phone interviews. Results: A total of 198 JAKi-treated patients were monitored for an average of 18.5 months. Nine subjects experienced HZ, resulting in an incidence of 2.95 per 100 patient-years. No demographic or treatment-related differences were found among patients who developed HZ and those who did not. Disease duration (OR: 1.06, 95% CI: 1.01-1.12), time on JAKi treatment (OR: 1.04, 95% CI: 1.009-1.073), higher disease activity at JAKi initiation (OR: 4.16, 95% CI: 1.07-16.17), and at 3-month follow-up (OR: 6.0, 95% CI: 1.35-26.60) were identified as predictors of HZ occurrence. Thirty-six patients received vaccination against HZ, and none reported adverse reactions or flare-ups during a mean follow-up of 9.6 months. Conclusions: The incidence of HZ aligns with published data, suggesting that disease and treatment duration, as well as disease activity, are significant predictors of HZ in RA patients on JAKi therapy. Vaccination against HZ proved to be safe and effective, underscoring its potential protective value in this patient population.

Subsequent biologic and targeted synthetic disease modifying anti rheumatic drugs after fulfilling difficult-to-treat rheumatoid arthritis criteria: a survival analysis.

To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation. Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention ratesin patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.

Detection of Sub-Clinical Tarsal Tunnel Syndrome in Rheumatoid Arthritis Patients

Abstract Background Asymptomatic or subclinical entrapments are common and frequent specially in patients with rheumatoid arthritis. Objectives Detection of sub clinical tarsal tunnel syndrome in rheumatoid arthritis patients and detect its correlation with disease activity and severity. Patient and Methods This case control was carried out on 16 patients with rheumatoid arthritis (RA) diagnosed according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria of 2010 and 16 healthy controls matched for age and sex. Assessment of disease activity was done by Disease Activity Score in 28 joints (DAS28) and Rheumatoid Arthritis Severity Scale (RASS). Electrophysiological studies were conducted on a two channel EMG machine, for each patient on both legs. Results No significant differences were noted between study groups regarding basal demographic and clinical manifestations. In rheumatoid patient, mean ± SD for disease activity score (DAS) was 4.11±0.51 versus 2.51 ± 0.66 in control patient with p &amp;lt; 0.0001. Regarding RASS, in rheumatoid patient, mean ± SD for disease activity was 28.94 ± 5.78; mean ± SD for functional impairment was 28.44 ± 5.46 and mean ± SD for physical damage was 31.75 ± 5.58 versus 11.44 ± 4.91, 13.88 ± 5.88 and 12.69 ± 4.24 in control group with statistically significant difference between both groups (p &amp;lt; 0.0001). In rheumatoid cases, all patients (100%) were affected on medial plantar nerve “sensory latency and amplitude” of right and left sides, also, all patients (100%) were affected on lateral plantar nerve “sensory latency” of right and left sides, while for amplitude right and left; 31.25% of patients were affected. Medial plantar nerves (motor latency) in both sides weren‟t affected in any patients, while for amplitude and nerve conduction velocity the percentage of patients in right and left was 100%. Lateral plantar nerve (motor latency and amplitude) weren‟t affected in any patients in both sides, while for nerve conduction velocity the percentage of patients in right and left was 100%. Posterior tibial nerves (motor latency and nerve conduction velocity) weren‟t affected in any patients in both sides, while for amplitude the percentage of patients in right and left was 6.25%. No correlation was detected between DAS and RASS as regard clinical, laboratory data and electrophysiological study in rheumatoid cases. This was clearly demonstrated by sensitivity and specificity test that medial and lateral plantar nerved (sensory and motor) were of highly significant value and posterior tibial nerve (motor) was of insignificant value in detection of sub clinical tarsal tunnel syndrome in rheumatoid arthritis patients. Conclusion Subclinical entrapments and sub clinical tarsal tunnel syndrome were detected in all rheumatoid arthritis patients using electrophysiological study and they were positively correlated with disease activity and severity. Also, most of joint complaints of rheumatoid arthritis patients as oedema and pain were due undiagnosed subclinical entrapments and sub clinical tarsal tunnel syndrome.

Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease.

Background/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.

Application of Immunoblot assay (ANA 23 Profile) for detection of autoantibodies in systemic sclerosis

Objective: Examine the clinical and subclinical characteristics and the rate of autoantibodies in systemic sclerosis (SSc) using Immunoblot technique (ANA 23 Profile). Research subjects and methods: Cross-sectional descriptive study of 57 patients diagnosed with SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria and were tested for autoantibodies using the Immunoblot technique (ANA 23 Profile) at the National Hospital of Dermatology and Venereology. Results: Among 57 SSc patients, the female/male ratio was 5/1. The average age of disease onset was 49.3±13.3, with 57.9% of patients over the age of 50. Diffuse SSc was the most common (70%). Raynaud was the most common symptom (98.2%), followed by gastroesophageal reflux (86%), and pulmonary fibrosis (70.2%). Heart and kidney damage were less frequently observed, accounting for 15.8 and 5.3%, respectively. Positive rates of the three major antibodies in SSc included anti-Scl-70 antibody (63.2%), anti-centromere antibody (17.5%), and anti-RNA polymer III antibody (12.3%), respectively. Scl-70 autoantibodies were mainly found in diffuse skin types (91.7%) while CENP autoantibodies were mainly found in localised skin types (90%) with p&lt;0.05. RNAP III antibodies were mainly found in diffuse skin types (85.7%), however, this difference was not statistically significant (p&gt;0.05). Conclusion: The presence of Scl-70 was related to the diffuse skin types while the presence of CENP was related to localised skin types.