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Fibromyalgia is characterized by diffuse musculoskeletal pain and fatigue. There are limited data about systemic steroid treatment of patients with fibromyalgia in the English literature. Patients with fibromyalgia with ongoing diffuse musculoskeletal pain despite standard treatment, extreme fatigue and elevated C-reactive protein (CRP) levels without evidence of synovitis, or other source of inflammation, were asked to participate in our study. After consent, demographic, clinical and laboratory parameters in addition to body mass index were documented. These patients were interviewed and asked to answer the Revised Fibromyalgia Impact Questionnaire (FIQR) just prior, 1 and 4 weeks following 14 mg depot betamethasone intramuscular injection. Twenty-three patients were recruited and 21 completed the study. 19 patients were women with mean age of 42±10.12 and CRP level of 14.1±3.96 mg%, and all had negative rheumatoid factor and antinuclear antibodies. All patients had significant improvement in all of the FIQR parameters, at 1 and 4 weeks, except memory, anxiety and balance. It can be concluded that systemic intramuscular depot betamethasone injection seems to have a favorable effect in patients with fibromyalgia with elevated CRP levels for at least 4 weeks.

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose–Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

Introduction Hemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV). Aim To evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients. Methods This is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28). Results The cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW > 14.85 had higher Disease Activity Score 28 (DAS28; p = 0.0003), ESR (p = 0.0001) and CRP (p = 0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV > 11.25 and Conclusion RDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost.

IntroductionAnti-Ro52/tripartite motif-containing protein 21 (TRIM21) IgG is one of the most common autoantibodies found in systemic autoimmune diseases and is typically found in conjunction with anti-Ro60 and/or anti-La. A retrospective, cross-sectional study was undertaken to examine the clinical and laboratory features of two serological subsets: patients with anti-Ro52/TRIM21 autoantibodies in the absence of anti-Ro60 and anti-La (isolated anti-Ro52/TRIM21) and patients with anti-Ro52/TRIM21 in the presence of anti-Ro60 and/or anti-La.MethodsOver a 12-month period, patients tested positive for anti-Ro52/TRIM21 via line immunoassay (LIA) at the Westmead Hospital (Australia) immunopathology laboratory were included. The presence of anti-Ro60 and/or anti-La via same LIA was noted. Associated laboratory and medical records were perused to extract demographic, laboratory, and clinical information.ResultsThere were 346 patients within the study period, and 39.9% of the patients positive for anti-Ro52/TRIM21 lacked anti-Ro60/anti-La autoantibodies. Isolated anti-Ro52/TRIM21 patients tend to be older, have lower anti-Ro52/TRIM21 titres, have lower rheumatoid factors, and have lower proportions of neutropaenia compared to patients who were positive for anti-Ro52/TRIM21 and anti-Ro60/La. This occurred independent to diagnoses of Sjögren’s syndrome or systemic lupus erythematosus. Coexisting neurological syndromes, pulmonary pathologies, and malignancies were more prevalent in the isolated anti-Ro52/TRIM21 subset.ConclusionsPatients with isolated anti-Ro52/TRIM21 tend to have distinct and important clinical and laboratory associations. It is unclear if these patients evolve or remain a stable subset and how they originate immunologically. Longitudinal and prospective studies are required to ascertain the overall predictive and prognostic value of this stratification.Key Points• Anti-Ro52/TRIM21 is an autoantibody found in autoimmunity and non-immunological conditions.• Sixty percent of anti-Ro52/TRIM21 patients are positive for anti-Ro60.• Isolated anti-Ro52/TRIM21 has reduced anti-Ro52/TRIM21 and rheumatoid factor titres.• Isolated anti-Ro52/TRIM21 is associated with anaemia and malignancies.

The aim of the Paediatric Rheumatology International Trials Organisation (PRINTO) juvenile idiopathic arthritis (JIA) classification criteria, which is still in development, is to identify homogeneous groups of JIA patients. This study was undertaken to compare International League of Associations for Rheumatology (ILAR) JIA classification criteria and PRINTO JIA classification criteria using data from the ReACCh-Out (Research in Arthritis in Canadian Children, Emphasizing Outcomes) cohort.We used clinicobiologic data recorded within 7 months of diagnosis to assign a diagnosis of JIA and identify subcategories of JIA among 1,228 patients according to the 2 JIA classification systems. We compared the proportions of patients classified and the alignment of classification categories with clinicobiologic subtypes and adult arthritis types.The PRINTO criteria classified 244 patients (19.9%) as having early-onset antinuclear antibody-positive JIA, 157 (12.8%) as having enthesitis/spondylitis-related JIA, 38 (3.1%) as having systemic JIA, and 10 (0.8%) as having rheumatoid factor-positive JIA. A total of 12% of patients were unclassifiable using the ILAR criteria, while 63.3% were unclassifiable using the PRINTO criteria (777 with other JIA and 2 with unclassified JIA). In sensitivity analyses,50% of patients remained unclassifiable using the PRINTO criteria. Compared to the PRINTO criteria, ILAR JIA categories aligned better with clinicobiologic subtypes in 131 patients (χCurrently identified PRINTO disorders can only be used to classify a minority of JIA patients, leaving a large proportion of JIA patients with other disorders requiring further characterization. Current PRINTO JIA classification criteria do not align better with clinicobiologic subtypes or adult forms of arthritis compared with the older ILAR classification system.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA.In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA.In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1β, IL-6, TNF-α, IL-8, and CCL5 levels in the samples.Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1β, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls.Overall, the findings suggested that IL-1β, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.

Introduction/objectivesPsychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient.MethodThis was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19-related stress, RA disease activity, and demographics. For the survey responders, anti-cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19-related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3).ResultsA total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors.ConclusionsThis study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti-citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non-CTD ILD.A total of 1570 non-CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA-ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant-free survival and incidence of progressive fibrosing-ILD (PF-ILD) were compared between seronegative non-CTD ILD (reference group), seropositive non-CTD ILD and RA-ILD using linear mixed-effect and Cox proportional hazards models adjusted for age, sex, smoking pack-years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow-up before and after the treatment.Two hundred and seventeen (13.8%) patients with seropositive non-CTD ILD had similar rates of FVC decline and transplant-free survival compared to seronegative non-CTD ILD, but more frequently met the criteria for PF-ILD (hazard ratio [HR] = 1.35, p = 0.004). RA-ILD had slower FVC decline (p = 0.03), less PF-ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non-CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non-CTD ILD.Seropositivity in non-CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression.

ObjectiveTo investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status.Methods1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson’s coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission).ResultsIn patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30–0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18–0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status.ConclusionsIn the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.

Background and objectives In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methods In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. Results Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ± 13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. Conclusions We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA.Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc.The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.

Palindromik romatizma (PR), eklemlerde kalıcı hasara neden olmaksızın alevlenmeler şeklinde ağrı, şişlik ve eritem ile karakterize klinik bir sendromdur. Literatürde, PR hastalarının %39-68’inde Romatoid faktör (RF) ve antisiklik sitrüline peptid (anti-CCP) antikor pozitifliği bulunmaktadır. Literatürde seropozitif ve seronegatif PR hastalarının klinik özelliklerini karşılaştıran çok az çalışma olup hala aydınlatılmamış birçok nokta vardır. Bu çalışmada kliniğimizde takipli PR tanılı hastaların demografik ve klinik özelliklerinin değerlendirilmesi, seropozitif ve seronegatif PR hastalarının karşılaştırılması planlandı. Çalışma retrospektif, kesitsel bir çalışma olarak tasarlandı. Otuz bir hasta tarandı ve dahil etme ve dışlama kriterlerini karşılayan 21 hasta çalışmaya alındı. Hastaların ortanca yaşı 43 yıl, ortanca takip süreleri 18 ay ve ortanca alevlenme süresi 3 gündü. Seronegatif grupta 12 hasta yer alırken seropozitif grupta 9 hasta mevcuttu. Seropozitif grubun ortanca yaş değeri daha yüksekti (55 yıl vs 42 yıl, p=0,023). Alevlenme süresi ve sigara içme süresi seropozitif grupta daha uzun olmasına rağmen istatistiksel olarak anlamlı bulunmadı (Sırasıyla, 4 gün vs 2 gün ve 28,3 paket/yıl vs 9,7 paket/yıl). Eşlik eden komorbideteler seronegatif hastalarda daha fazla olmasına rağmen istatistiksel olarak anlamlı değildi. Ortalama lenfosit değerleri ise seropozitif grupta anlamlı daha yüksekti (p=0,037). Sonuç olarak, seropozitif PR hastalarının ortanca yaşları negatif olan hastalara göre daha yüksek olduğu ve ortalama lenfosit değerlerinin seropozitif hastalarda daha yüksek olduğu bulundu., Palindromic rheumatism (PR) is a clinical entity, which is characterized by remittent flares of pain, swelling and erythema around the joints that do not lead to persistent damage. In the literature, the frequencies of rheumatoid factor (RF) positivity and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity have been reported as 39-68% in patients with PR. To our knowledge, studies investigating the comparison of clinical features of seronegative and seropositive patients are scarce. We aimed to assess demographic data and clinical characteristics of PR patients who followed in our clinic and to compare these features between seronegative and seropositive patients. The current study was designed as retrospective and cross-sectional. Thirty-one patients were screened and 21 patients who met the inclusion and exclusion criteria were included in the study. The median age, median follow-up duration, and median flare duration were 43 years, 18 months, and 3 days, respectively. Twelve patients were in seronegative group while 9 patients were in seropositive group. The median age was higher in seropositive patients than in seronegative patients (55 vs. 42 years, p=0.023). Even though the duration of flare and smoking cigarette were higher in seropositive group, there was not statistically significant difference between groups (4 vs. 2 days and 28.3 vs. 9.7 packs/years, respectively). Comorbidities were common in seronegative patients but there was not statistically significant difference between groups. Mean lymphocyte count was statistically significantly higher in seropositive group (p=0.037). In conclusion, the median age and mean lymphocyte count were higher in seropositive group than in seronegative group.

Objective.Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity.Methods.Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire–Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28).Results.Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77–0.91] for RF and OR 0.88 [95% CI 0.81–0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity.Conclusion.Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF

Patients with established rheumatoid arthritis (RA) demonstrate altered immune responses to Epstein-Barr virus (EBV), but the presence and roles of EBV have not been fully explored during the pre-clinical disease period. This study was undertaken to determine if EBV infection, as evidenced by an altered anti-EBV antibody response, either plays an important role in driving the development of RA or is a result of expanded RA-related autoimmunity.A total of 83 subjects with RA according to the 1987 American College of Rheumatology (ACR) criteria and 83 age-, sex-, and race-matched control subjects without RA were included in our study. We collected sera from RA subjects and matched controls during the pre-RA and post-RA diagnosis periods and tested the sera for the presence of 5 anti-EBV antibodies (anti-EBV nuclear antigen 1 IgG isotype, anti-viral capsid antigen [anti-VCA] isotypes IgG and IgA, and anti-early antigen [EA] isotypes IgG and IgA), 7 RA-related autoantibodies (rheumatoid factor measured by nephelometry [RF-Neph] as well as isotype-specific IgA-RF, IgM-RF, and IgG-RF, and anti-cyclic citrullinated peptide [anti-CCP] antibodies, including anti-CCP2, anti-CCP3, and anti-CCP3.1), 22 cytokines/chemokines, 36 individual anti-citrullinated protein antibodies, and IgG-cytomegalovirus (CMV) antibodies. Random forest classification, mixed modeling, and joint mixed modeling were used to determine differences in anti-EBV antibody levels between RA subjects and controls.Random forest analysis identified the presence of preclinical EBV antibodies in the serum that differentiated RA subjects from controls without RA. Specifically, IgG-EA antibody levels were higher in RA subjects (mean ± SD 0.82 ± 0.72 international standardized ratio [ISR]) compared to controls (mean ± SD 0.49 ± 0.28 ISR). In subjects with RA, elevated serum IgG-EA levels in the preclinical period before seroconversion were significantly correlated with increased serum IgM-RF levels (P = 0.007), whereas this correlation was not seen in control subjects without RA (P = 0.15). IgG-CMV antibody levels did not differ between groups.Subjects whose serum IgG-EA antibody levels are elevated in the preclinical period will eventually develop RA, which suggests that EBV reactivation cycles are increased during the preclinical period of RA. A combination of RF and EBV reactivation may play an important role in the development of RA.

Palindromic rheumatism (PR) is characterized by self-resolving and short duration attacks of arthritis/periarthritis. The present study was performed to report the results of PR treatment with methotrexate (MTX).We reviewed the charts of 152 patients with diagnosis of PR. Inclusion criteria were diagnosis of PR according to the criteria of Weismann, age ≥16, active disease and treatment with MTX for at least 6 months. Disease outcome was assessed by reaching remission and prevention of disease evolution to chronic arthritis. Remission was defined as stopping the attacks for 12 weeks and prednisolone dose ≤5 mg/d. MTX treatment failure was defined as failure to achieve remission, the need to add other disease-modifying antirheumatic drugs and disease progression to chronic arthritis.Fifty-nine patients were included in the study. Median duration of follow-up was 43 months. Attacks were controlled in 89.8% of patients. In 80% of the patients remission occurred during 12 months after starting treatment with MTX. Treatment failed in 20.3% of patients. Wrist joint involvement and positive rheumatoid factor (RF) were significantly more common in the MTX treatment-failed group. In RF positive patients evolution to rheumatoid arthritis was more common than in RF negative patients. No significant differences were observed in remission rate and evolution to rheumatoid arthritis in anticitrullinated C peptide positive and negative patients.The present study, demonstrated the efficacy of MTX in controlling PR in seropositive and seronegative patients over a median of 43 months of treatment.

Erosive Hand OsteoArthritis (EHOA) is a common rheumatological problem. We aim to determine characteristics of EHOA patients: comorbidities, radiographic erosivity and pain experienced after being diagnosed, in order to find which of these are potentially relevant in upcoming interventional trials.Retrospective analysis of EHOA patients within the electronic database in one centre, with a telephone interview on pain as experienced even exceeding 12 months after being diagnosed.Eighty-four non-academic EHOA patients were found: 89% females (median age 69 years), 11% males (similar age distribution). Kellgren-Lawrence (KL) erosivity scores in both sexes were comparable; DIPs scored higher than PIP's. Comorbid conditions were crystal-induced arthritis, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in 8%, 5% and 1%, respectively; seropositivity for rheumatoid factor and anti-citrullinated protein antibodies in 8% and 1% respectively. Pain worst experienced often exceeded a visual analogue score of 5.0, but was unrelated to the total KL score. Some pain reduction was reached with non-steroidals (perorally/transcutaneously) as deduced from continued use in 1 in 3.In many EHOA patients, there is an unmet need regarding the treatment of pain, which per se was not directly correlated with erosivity score. Future studies may be designed considering the aforementioned characteristics, acting on the inflammatory process resulting in PIP/DIP erosions, with the exclusion of RA and PsA in order to get a clean study on EHOA. Several studies with monoclonal antibodies have been performed but demonstrated ineffectivity on the outcome of pain. Hope glooms with the arrival of innovative small molecules that may reach EHOA target cells. Key Points • Erosive handOA is a common problem in non-academic rheumatology; it is often associated with significant pain in both sexes exceeding a VASpain of 5.0 even years after being diagnosed; 1 in 3 found some relief in non-steroidals perorally/transcutaneously. • Future studies will have to focus on (episodic) inflammatory hand OA resulting in proven erosivity (EHOA) located in PIP plus DIP joints and may have to exclude comorbid active crystal-induced arthritis as well as rheumatoid/psoriatic arthritis and possibly even RF/ACPA seropositivity in order to get a clean study on EHOA. • As several big monoclonals have failed in EHOA, we may have to search for promising new drugs within the group of small molecules. These will have to show a significant pain-reducing effect and preferably also a disease-modifying osteoarthritis drug (DMOAD) effect.

Background. Rheumatoid arthritis (RA) belongs to the most common inflammatory diseases of the joints, and in its pathogenetic constructions, a certain role is played by the changes in the autonomic nervous system (ANS). Aim of the study: to evaluate the vegetative passport in RA, the incidence and nature of vegetative dysfunction (VD) in different types of the disease, the relationship with the parameters of variation pulsometry. Materials and methods. There were examined 173 patients with RA aged 18 to 79 years (an average of 46 years), among them there were 21 % of males and 79 % of females. The duration of the disease was 10 years, type of RA, seropositive in terms of rheumatoid factor and citrulline antibodies, was detected in 3/4 of cases, extra-articular (systemic) form of the disease was diagnosed in 37 % of observations, osteoporosis was found in 67 % of patients. Results. VD is observed in 20 % of RA patients, mainly in those with seropositive variant of the disease that is associated with higher values of bone mineral density, larger changes in the variation pulsometry, with the influence on the integral nature of articular syndrome and the rate of involvement in the pathological process of elbow and hip joints, and the severity of autonomic disorders is closely linked to the presence of intra-articular arthrocalcifications, digital arteritis and dyscirculatory encephalopathy. Vegetative passport defines the integral clinical and laboratory and instrumental RA symptoms, while the ANS type is affected by the seropositivity of the disease and the bone density, with the highest level in cases of vagotonia, when VD directly correlates with the joint pathology progression rate, and in sympathicotonia — with intial parameters of rheumatoid factor and arthritis activity, also, regardless of the vegetative status, there are variance-correlation ratios of specific parameters of RA course and variation pulsometry. Conclusions. VD occurs in every fifth patient with RA, is associated with the peculiarities of the articular syndrome course and extra-articular signs of the pathological processes, is involved in disease pathogenesis constructions, and in the future it will be useful to identify actively ANS changes for subsequent timely rehabilitation.

Relevance. Rheumatoid arthritis (RA) belongs to the most common inflammatory diseases of the joints, and the number of patients with this pathology increases everywhere, causing enormous medical, social and economic damage. An important role in the pathogenesis of RA is given to dysfunctions of the autonomic neural system (ANS), which condition is closely related to the bone metabolism and bone mineral density. The purpose and objectives: to assess the incidence of osteoporosis at different «vegetative passport» of RA patients, to explore the relationship of vegetative dysfunction (VD) signs with the nature of bone density. Material and methods. There were examined 173 patients with RA aged 18 to 79 years (average age — 46 years), among them 21 % males and 79 % females. The duration of disease manifestations was 10 years, variation of RA, seropositive for rheumatoid factor and citrulline antibodies, was detected in 3/4 of cases, extraarticular (systemic) form of the disease was diagnosed in 37 % of cases. Results. Osteoporosis develops in 2/3 of RA patients, and its pathogenic constructions are closely associated with the presence of VD, the severity of which is correlated with indicators of bone density, and those, in turn, — with parameters of variation pulsometry, activity and bone-destructive components of articular syndrome, depends on the vegetative type of patients (vagotonia is more typical for patients with osteoporosis, and for the rest of the patients — sympathotony). The imbalance of bone metabolism markers in RA patients enhances the existing violations of ANS, and the content of magnesemia has prognostic value in relation to VD. Its severity correlates with the severity of osteoporosis, wherein unfavorable prognostic indicators are blood calcium level more than 80 mg/l and alkaline phosphatase activity over 180 U/l. Conclusion. The development of osteoporosis is associated not only with features of the articular syndrome course and extraarticular RA symptoms, but also with the state of the ANS, which is involved in the pathogenetic constructions of bone density reduction and imbalance of bone metabolism markers. In the future, the active identification of VD will be useful for subsequent timely rehabilitation.

Aim of the work To evaluate the demographic, clinical presentation, and laboratory findings of the juvenile idiopathic arthritis (JIA) subtypes in Sudanese patients attending the Pediatric Rheumatology Clinic. Patients and methods This single-center study was conducted at the Rheumatology Clinic of Ahmed Gasim Hospital, Khartoum North. A specially designed data collection form was used. Full medical history and physical examination of patients was done. The initial investigation was collected from the patients' records. Results Eighty-one patients were enrolled in the study. Females were 54 and 27 males (F: M was 2:1). The mean age of the patients was 10.8 ± 3.6 years, 58% were above 10 years; disease duration 5.8 ± 2.4 years and age at onset 9 ± 3.8 years, the commonest age at onset was between 5 and 10 years. Half of the patients were from rural areas. There was a positive family history in 7.4%. Morning stiffness was the commonest presenting symptom (98.8%) and uveitis was present in 8.6%. The knee was the most affected joint (82.7%). The polyarticular subtype was found in 51 (63%), systemic-onset in 18 (22.2%), oligo articular in 10 (12.3%) and spondyloarthritis in 2 (2.5%). Seven patients (8.6%) had uveitis. Rheumatoid factor (RF) and antinuclear antibody (ANA) were positive among 30.9% and 46.9% of the participants respectively. Conclusion Females predominate and half of the patients are from rural areas. Polyarticular is the commonest subtype. Morning stiffness is the presenting symptom. The knee joint was the most affected. Positive RF was found in one-third of patients, ANA in about half of them.

Aim of the work To analyze the relationship between miRNA-146a rs2910164 and rheumatoid arthritis (RA) susceptibility and clarifying its association with disease activity and extra-articular involvement. Patients and methods The study enrolled 50 RA patients and 40 controls. DNA extraction from whole blood was done. Genotyping was performed by real-time polymerase chain reaction. The selected single nucleotide polymorphism was rs2910164 in the miRNA-146a gene. Genotyping was performed on genomic DNA samples by allelic discrimination assay. Disease activity score (DAS28) and health assessment questionnaire-disability index (HAQ-DI) were assessed. Results The mean age of patients was 44.8 ± 9.9 years while age at onset was 37.2 ± 9.8 years. Female:male was 5.3 vs 1. Females had significantly higher DAS28, visual analogue scale and rheumatoid factor (RF) than males (p = 0.04, p = 0.009, p = 0.03). The frequency of GC genotype was more in both males and females (62.5 vs 47.6%). GC genotype and G allele were the most frequent in patients. No significant difference in the frequency distribution of genotypes and alleles was observed between patients and controls. There was a significant difference in the number of swollen joints (p = 0.04) and sicca symptoms (p = 0.01) being higher in those with CC genotype with a tendency of increased DAS28, HAQ-DI, deformities and rheumatoid nodules with CC genotype and interstitial pulmonary fibrosis and RF with GG genotype. Conclusions CC genotype was associated with sicca symptoms and swollen joints, deformities, disease activity and functional disability. miRNA-146a may be a potential biomarker for extra-articular manifestations of RA that need more attention and warrant aggressive therapy.

To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity.From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed.One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients.Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.

Post Translational Modification (PTM) is a process in which covalent addition of functional groups on protein occurs to maintain their structure, function and stability. Every PTM process in our living system occurs to enhance the functional diversity of a protein. But sometimes, it occurs without any regulation and that might lead to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects the joints. Proper treatment can make the symptoms manageable for RA, but it is not curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as the liver, kidney, etc. Early diagnosis of RA is necessary to manage the aggressive symptoms. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Besides citrullination, several other PTMs are also involved in the generation of autoantibodies, such as carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, and lipidation. The aim of this review is to elucidate several changes in the form, nature, and function of PTMs in RA. This review will give a recent overview on the role of PTMs in the pathogenesis of RA with a focus on the post-translational modifications.

Objectives Whether the characteristics of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) have changed in the era of biologic disease-modifying antirheumatic drugs (bDMARDs) is unclear. We compared the radiographic findings of the knees in TKA recipients with RA before and after the introduction of bDMARDs. Methods Consecutive patients who underwent primary TKA between 1999 and 2002 (115 knees; 79 patients, group A) and between 2013 and 2017 (117 knees; 95 patients, group B) were retrospectively evaluated. Clinical data, including disease duration, medication, C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were collected. The Larsen classification, joint space narrowing (JSN), bone erosion, and geode and osteophyte formation were evaluated on preoperative radiographs. Results Osteophyte formation was significantly increased, and bone erosion and geode formation were significantly decreased in group B. In addition, medial-dominant JSN was significantly increased, and bicompartmental JSN was significantly decreased in group B. Medial-dominant JSN was positively and bone erosion was negatively associated with osteophyte formation. Conclusions Following the introduction of bDMARDs, typical radiographic findings of rheumatoid knees have decreased, and secondary osteoarthritis-like changes, characterized by osteophyte formation and medial-dominant JSN, have increased in the knees of TKA recipients.

PURPOSE Beneficial effect of long-chain ω-3 fatty acids against symptoms of rheumatoid arthritis (RA) has been indicated in previous studies. We examined the effect of flaxseed and anti-inflammatory diet in patients with RA. METHODS The 12-week intervention was performed on 120 patients with RA who were randomized to three groups of flaxseed (30 g/day) plus anti-inflammatory diet (AIF group), flaxseed (30 g/day) plus regular diet (RF group), and roasted wheat (30 g/day) plus regular diet (RW group). Disease Activity Score 28-joints (DAS28), health assessment questionnaire (HAQ) disability and pain, quality of life, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and anti-cyclic citrullinated peptides (anti-CCP) were measured before and after trial. Analysis was performed using per-protocol and intention-to-treat (ITT) approaches. RESULTS One hundred and two patients completed the protocol. Flaxseed decreased DAS28 in RF group compared to RW (- 0.87 ± 1.11 vs. - 0.24 ± 0.78; P = 0.014). Pain severity (P ≤ 0.001), morning stiffness (P

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that impact daily life activities. The impact on work productivity is critical because of persistent work disability. Aim: To evaluate work productivity in RA patients compared to healthy controls, and to assess the impact of socio-demographic characteristics on work productivity. Methods: This was a case-control study conducted at the Rheumatology Unit of Baghdad Teaching Hospital, Medical City during the period from August 2020 to the end of March 2021. Seventy-two patients with RA were selected and compared with 72 healthy subjects as a control group. All patients were diagnosed according to ACR/EULAR 2010 RA classification criteria. The socio-demographic and clinical features, lifestyle practices, and disease activity of the patients and controls were all recorded during interviews. A standardized Arabic version of the Workplace Activity Limitation Scale (WALS) and the Job Limitations Questionnaire were used to assess the impact of RA on work productivity (WLQ-25). Results: The vast majority of patients were females (58.1%). Positive rheumatoid factor was reported in 94.4% of the patients. The patients showed a significantly lower WALS total score and higher WLQ-25 total score median (IQR) compared with controls. Conclusion: Active RA impairs the work productivity which was influenced by CDAI score and negatively associated with the use of DMARDs.

Background: Rheumatoid arthritis is the most common cause of inflammatory polyarthritis. Interleukin‐37 (IL-37) has been found to play an important regulatory role in the development of inflammatory diseases. Objectives: To assess serum IL-37 level in rheumatoid arthritis (RA) patients compared to controls, to evaluate its diagnostic and predictive utility in RA patients and to investigate IL-37 level correlation with demographic and clinical characteristics of RA. Methods: Eighty subjects, 40 RA patients aged between 23-63 years and 40 healthy controls aged between 28-67 years were evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum IL-37 levels. Results: Serum IL-37 was significantly higher in RA patients compared to healthy controls. At optimum cut off value of >58.275 pg/ml, serum IL-37 had 100% accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. Serum IL‐37 level was not significantly related to Disease Activity Score of 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), also not correlated with C-reactive protein(CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). Also there was no correlation between the level of IL-37 and treatment. Conclusions: IL-37 was significantly higher in RA patients compared to healthy controls with a high diagnostic and predictive ability, and may be a potential biomarker for diagnosis and prediction of RA.

Rheumatoid Arthritis or RA disease is a chronic inflammatory and systemic disease associated with broad synovitis resulting in erosion of the articular cartilage and marginal bone causing joint damage. RA is an autoimmune disease with the discovery of an autoantibody, namely rheumatoid factor. The relevant antibody is anti-citrullinated protein (ACPA) antibody. Citullination on the introduction of several proteins such as fibrin, vimentin, fibronectin, collagen type II, which is expressed in the synovial membrane during inflammation by ACPA. In a recent study increased HDAC activity in the synovial tissue of RA patients has increased. Histone deacetylase or abbreviated as HDAC is an enzyme that is important in regulating gene transcription by altering the acetylation of histone proteins which results in an important regulation of repression in the implementation of inflammation. HDAC enzyme inhibitor (HDACi) is an HDAC enzyme inhibitor that can provide benefits for the treatment of various diseases including malignancy and inflammation. In inflammatory disease HDACi overcomes inflammatory cytokines such as TNF-α, IL-6 and IL-1β. One of the HDAC classes is HDAC1 which is highly expressed in the synovial fibroblasts of RA patients. HDACi can burden swollen joints, reduce mononuclear cell infiltration, request pannus orders, inhibit bone and cartilage damage.

The article presents modern ideas about etiology, hereditary predisposition, immunopathogenesis of juvenile rheumatoid arthritis (JRA), one of the most frequent and most disabling rheumatic diseases in children. The etiology of the disease isn’t finally determined. There are only a number of more or less well-founded hypotheses. Among the predisposing factors, an important role belongs to persistent viruses. Arthrotropic persistent viruses — Coxsackie, Epstein-Barr virus, cytomegalovirus, herpes, parvoviruses which have tropism to the joint tissues, can persist for a long time in them, and cause immune inflammation on the background of immunological defects. There is also evidence of a link between JRA and infection caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae. Genetic predisposition and the features of the immune system play a role in the emergence and development of JRA. There is information about the association of HLA histocompatibility genes with JRA in general and with specific variants of the disease. HLA A2, DR5, DR8 are markers of oligoarthritis in girls with uveitis, with seropositivity in antinuclear factor. HLA B27 is a risk marker for JRA developing in boys with oligoarthritis or localized polyarthritis, with predominant lesion of the lower limb joints, with the presence of enthesopathies in school age or adolescence. HLA DR4, DR5, DRB1-04 are markers of JRA in girls with lesions of small symmetrical joints of the hands, seropositive for rheumatoid factor, with the onset of the disease in the senior school age. The defects of T- and B-cell immune are the basis of the pathogenesis of JRA reactions leading to hyperproduction of proinflammatory cytokines. Hyperproduction of proinflammatory cytokines underlies the damage to the synovial membrane of the joint, cartilage, as well as the development of systemic manifestations of the disease. Among a large number of proinflammatory cytokines, the tumor necrosis factor a (TNF-a), interleukins (IL) — 6, 1β, play a key role in the development of the disease. TNF-a leads to chronic inflammation, destruction of the cartilage and bone. IL-6 has an exceptional role in the genesis of the systemic variant of the disease. With its hyperproduction, such extraarticular manifestations of the disease as fever, hypochromic anemia, thrombocytosis are associated. IL-6 stimulates the production of acute-phase proteins by hepatocytes, plays a role in the development of a number of complications, such as osteoporosis and amyloidosis. The state of the cytokine network under various variants of the JRA is not fully studied. Some authors point to the maximum increase in IL-6 and IL-1 in the systemic variant of the disease. A significant increase in TNF-α was detected in patients with polyarticular JRA, especially with high rheumatoid factor values. The level of proinflammatory cytokines correlates with inflammation activity and reflects the severity of the disease, determines a further prognosis. In the development of rheumatic diseases in children, an important role is played not by the absolute amount of certain cytokines, but by the imba-lance of pro- and anti-inflammatory cytokines. This imbalance can arise under the influence of damaging factor: bacterial or viral infection, hypothermia, insolation, preventive vaccinations, joint trauma, adverse environmental factors, chronic psychoemotional stresses. But in most children, after the elimination of damaging factor, the normal ratio of cytokines is restored, and in children with genetic predisposition, the imbalance persists that leads to the development of rheumatic pathology.

Background. The prevalence of rheumatoid arthritis (RA) among the world’s population is about 1 %, and among certain populations of people it reaches 5–7 %. The risk factors for the development and high rates of RA progression include high concentrations of quartz (silicon (Si) dioxide) in the inhaled air, the toxic effect of which is considered as one of the most powerful pathogenetic factors of this disease. The purpose of the work was to evaluate the clinical and pathogenetic significance of silicon microelementosis in RA. Materials and methods. Eighty-three patients with RA were examined (22 % were males and 78 % — females aged from 22 to 75 (mean of 45) years). The duration of the disease from the first signs of its manifestation was 9 years. Systemic form of the disease was diagnosed in 19 % of cases, RA seropositive for rheumatoid factor was detected in 68 %, for cyclic citrullinated peptide antibodies — in 80 % of individuals. The content of Si in the blood serum and in 19 patients — in cerebrospinal fluid was determined using an atomic absorption spectrometer SolAAr-Mk2-MOZe with an electrographite atomizer (Great Bri­tain). Using a computer tensiometer PAT2-Sinterface (Germany), the parameters of the surface tension of blood serum and synovial fluid were investigated with a surface life time of 0.01 sec and tending to infinity, and their ratio was calculated. Results. RA is accompanied by the absence of probable changes in the level of silicon. Si microelementosis is associated with the clinical, radiographic and sonographic signs of the disease course, the degree of activity and severity of arthritis, and silicon imbalance is involved in the pathogenesis of the articular syndrome, damage to the ske­letal muscle, the peripheral nervous system, wherein, Si indicators in blood may have prognostic significance.

ObjectiveWe aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk.MethodsThis case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus (“seropositive” was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking.ResultsWe identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05–2.45), chronic sinusitis (OR 2.16, 95% CI 1.39–3.35), and asthma (OR 1.39, 95% CI 1.03–1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08–1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02–2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01–5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02–2.27, P = 0.10 for interaction).ConclusionAcute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.

Background: Pediatric rheumatic diseases can cause considerable disease burden to children and their families. They are associated with the potential for physical disability, diminished quality of life and significant direct and indirect costs. Objective: We aimed to describe the clinical spectrum and the frequencies and different patterns of Juvenile idiopathic arthritis (JIA) in children in Zagazig University Hospitals. Patients and methods: A cross-sectional study included 68 cases with Juvenile idiopathic arthritis < 16 years. The study was conducted over two years from December 2017 to December 2019. Investigations as complete blood count, C reactive protein, antinuclear antibody (ANA), rheumatoid factor (RF), complement C3 & C4, creatine phosphokinase, and EMG. Management and treatment plans were achieved and data about the results were collected. Results: Most of patients diagnosed with rheumatological diseases were females. Oligoarticular JIA was the commonestsubtype of JIA in our study followed by polyarticular then systemic onset type. NSAIDs was the commonest drug used by JIA patients followed by methotrexate then corticosteroids. Conclusion: Early diagnosis and effective management of these children is essential so that they can lead a normal or near normal life especially in patients with rheumatological diseases with chronic morbidity as JIA.

Background. The trigger factors of the development of rheumatoid arthritis (RA) may be infections associated with the carriage in the oral cavity of Actinomycetes, Campylobacter, Mycoplasma, Porphyromonas, Transducers, Proteus, Selemons, Streptococci, and Fusobacteria, but their role in the disease pathogenesis requires clarification. In turn, the quantity of cases of comorbid infectious pathology significantly increases in RA. The purpose was to study the qualitative and quantitative composition of the oral microbiota in RA, to assess the role of individual bacteria in the pathogenetic structures of the disease. Materials and methods. There were examined 121 RA patients aged 18–76 years (on ave­rage 49 years old), among whom there were 19 % men and 81 % women. The duration from the first manifestation of the disease averaged 10 years. The frequency of seropositivity of RA for rheumatoid factor in the blood was 81 %, and for antibodies to cyclic citrullinated peptide — 75 %. I, II, and III degrees of disease activity were determined in 13, 45, and 42 % of cases, respectively, and the ratio of I, II, III, and IV stages of the pathological process was 1 : 5 : 5 : 3. To assess the number of aerobic and facultative anaerobic microorganisms growing on the gingival mucosa, the technique of sterile paper discs was used. The kits “Mikro-La-Test”, “Streptotest-16”, “Anaero-Test 23”, “Neferm Test 24” were used. Results. The vegetation of associations of aerobes on the gums was found in 96.7 % of patients, anaerobic bacteria — in 91.7 %, the number of which is closely related to clinical, laboratory, and X-ray signs of RA, while the integral landscape of the gingival microbiota is influenced by the severity of the comorbid chronic generalized periodontitis, which affects the presence of Moraxella, Sarcina, Streptococci, and Eubacteria in the oral cavity, moreover, the number of anaerobes reflects the degree of RA activity and bone mineral density, and in the pathogenetic constructions of individual signs of the disease (the nature of the articular syndrome and damage to the periarticular tissues), Aerococci, Candida, Clostridia, Megasphaera, Propionibacteria, Sarcina, Fusobacteria, and Eubacteria are involved. Conclusions. The obtained data dictate the need to develop new approaches to medical techno­logy for individual etiopathogenetic therapy of RA with comorbid periodontitis, to identify criteria that allow assessing the activity of the pathological process, predicting the nature of the course of the disease and the effectiveness of therapeutic measures.

Objective To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability. Results The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years. Conclusion The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.

Background. Hemorrhagic vasculitis, or Henoch-Schonlein purpura (HSP), in children has its onset in the form of the articular syndrome in the vast number of patients, which is a part of the diagnostic criteria of this disease. The nature of the arthritis after the disease transformation from the juvenile HSP remains unexplored. In adulthood, articular patho­logy can manifest as migratory intermittent or chronic arthritis, but this information should be clarified. The objective was to study the clinical, X-ray and sonographic features of arti­cular syndrome course in patients with HSP and to evaluate the features of arthropathy in the presence of the disease that began in childhood and adulthood. Materials and methods. The study included 174 patients with HSP (83 % of men and 47 % of women). Childhood-onset vasculitis (on average in 12 years) was diagnosed in 92 patients, and adulthood-onset (on avera­ge in 25 years) — in 82; I, II and III degree of activity of the pathological process are established at a ratio of 1 : 2 : 2. Results. The joint affection is observed in every second patient with HPS, which is closely related to the patient’s age at the onset of the disease, duration and degree of the activity of pathological process, seropositivity by the high content of immunoglobulin A and rheumatoid factor. At that, clinical, radiological and sonographic nature of the articular syndrome’s course (involving the wrist, hip and sacroiliac joints, the development of aseptic osteonecrosis, bone erosion, meniscitis and intraarti­cular cartilage flaps) depend on extraarticular manifestations of the di­sease (lesion of heart, kidney, pancreas, central nervous system). They are accompanied by an increased concentration in the blood of β2-microglobulin and circulating immune complexes that together with the values of fibrinogenemia have predictive value. Dimorphism of HSP, transformed from a juvenile one, is characterized by the less serum levels of fibronectin, circulating immune complexes and rheumatoid factor. Conclusions. The changes in the joints, regardless of the age of patients at the onset of HSP, occur with the same rate in every second case, but arthropathy in adults is more severe with joining of the additional clinical, radiographic and sonographic features.

Актуальність. Анкілозуючий спондиліт є хронічним прогресуючим системним автоімунним ревматичним захворюванням хребта, периферичних суглобів, крижово-клубових зчленувань, ентезисів, зв’язкового апарату й внутрішніх органів, належить до факторів ризику тяжкої судинної патології. Мета дослідження: вивчити при анкілозуючому спондиліті клініко-інструментальний перебіг ангіопатії, з’ясувати патогенетичні зв’язки з імунними показниками. Матеріали та методи. Під наглядом перебували 79 хворих віком від 15 до 66 років (в середньому 38 років), серед яких чоловіки становили 95 %, жінки — 5 %. Тривалість хвороби від перших її проявів дорівнювала 11 рокам, І ступінь активності відмічався в 32 % спостережень, ІІ — у 39 % і ІІІ — у 29 %, а співвідношення повільнопрогресуючого та швидкопрогресуючого перебігу патологічного процесу становило 4 : 1. Периферичний моноолігоартрит констатовано в 47 % від числа хворих, поліартрит — у 53 %. Пацієнтам виконували ехокардіографію, ультра­звукову допплерографію судин й біомікроскопію судин кон’юнктиви. Результати. Ангіопатія спостерігається у 85 % від числа хворих на анкілозуючий спондиліт, розвиток якої прямо пов’язаний зі ступенем активності патологічного процесу й обернено — із серопозитивністю за ревматоїдним фактором. Шкірний васкуліт залежить від віку пацієнтів, увеїт, склерит, синдром Рейно, ураження центральної та периферичної нервової системи — від особливостей перебігу суглобового синдрому. Інтегральні клінічні й інструментальні судинні показники вірогідно співвідносяться з імунними параметрами — рівнями ревматоїдного фактора, С-реактивного протеїну, циркулюючих імунних комплексів, значеннями імуноглобулінемії, а ураження судин перебігає з підвищенням значень легеневого артеріального тиску та судинного опору, у генезі яких бере участь C-реактивний протеїн, що має прогностичну значущість.

Background. Rheumatoid arthritis (RA) belongs to the most common inflammatory diseases of the joints, and the number of these patients is increasing everywhere causing enormous medical, social and economic damage. An important role in the pathogenesis of RA is given to the violations of the autonomic neural system (ANS) functions, whose condition is closely related to the rheological properties of the blood serum (RPBS). The purpose and objectives. To evaluate the correlation between «vegetative passport» of RA patients and autonomic dysfunction with RPBS at different variations of the disease. Materials and methods. We have examined 173 patients aged 18 to 79 years (on the average 46 years), among them 21 % were males and 79 % — females. The duration of disease manifestation was 10 years, type of RA seropositive for rheumatoid factor and citrulline antibodies was detected in 3/4 of cases, extraarticular (systemic) form of the disease was diagnosed in 37 % of cases. The surface indicators of the blood serum — viscosity, elasticity, tension, relaxation and viscoelasticity modulus — were determined using digital tensio­meter PAT2-Sinterface (Germany). Results. «Ve­getative passport» defines the integral clinical, laboratory and instrumental signs of RA, wherein the severity of autono­mic dysfunction is directly correlated with the rate of joint pathology progression, and in sympathicotonia — with the baseline parameters of rheumatoid factor in the blood and the degree of RA activity. Changes in RPBS are accompanied by an increase in the steady-state (static) surface tension, which are recorded in 70 % of cases. Integral state of interfacial activity, relaxation and viscoelastic characteristics of the blood determine the type of ANS and the presence of autonomic dysfunction in patients (patients with vagotonia are characterized by increase in viscoelastic modulus and decrease of surface tension, with sympathicotonia — by increase in surface tension and reduced surface viscosity). RPBS parameters are associated with the severity of autonomic disorders, and the surface viscosity index has a prognostic value. Conclusions. The development of autonomic dysfunction is correlated not only with the features of the course of articular syndrome and extraarticular RA symptoms, but also with the state of ANS, which is involved in RPBS disorders. In the future, the assessment of ANS state will be useful for subsequent timely rehabi­litation measures of the disease.

Articular syndrome is one of the main signs of the microscopic polyangiitis (MPA), which in some regions of the Earth accounts for over 90 % of all systemic vasculitis (SV), associated with antineutrophil cytoplasmic antibodies (ANCA). It was found that 5 years after the manifestation of MPA, a progressive reduction of the para-articular (epiphyseal) bone mineral density and destruction of the joints begin to form. Many questions related to the nature of the course of joint pathology in specific ANCA-SV require further study. Objective: to evaluate joint damage in patients with MPA and the relationship with extra-articular pathology. Material and methods. We study involved 89 patients with MPA aged 18–78 years old, among which there were 44 % men and 56 % women. The duration of the disease from the first signs of manifestation was 7 years. Acute or subacute course of MPA has been registered in 27 % of cases, and in the rest — chronic one; I degree of the activity of pathological process has been detected in 10 % of cases, II —in 32 %, III — is 58 %. Results. The joint involvement is observed in 60 % of patients with MPA, in 40 % of cases it occurs in the form of oligoarthritis, depends on the presence of pathology in skeletal muscles, pneumopathy or peripheral neuropathy. Clinical, radiological and sonographic signs of articular pathology in MPA are closely associated with patients’ age, disease duration, lesions of the heart, kidneys and skin. In the pathogenetic structures of arthropathy in patients with MPA, C-reactive protein (CRP) and circulating immune complexes (CIC) are involved, and the nature of ANCA (antibodies to myeloperoxidase and proteinase-3) is of small value, while the high blood levels of rheumatoid factor (RF) have certain prognosis-negative significance in terms of the severity of joint pathology. Conclusion. Unfavorable prognostic criteria for the development of joint pathology in patients with MPA are indicators in the blood: CRP > 20 mg/l and CIC > 130 с.u., and the RF values > 60 IU/ml are considered the risk factors for severe arthropathy.

Background. Juvenile idiopathic arthritis (JIA) is characterized by chronic inflammation of the joints with progressive course and a strong tendency to development of early disability. Long-term follow up of a patients with JIA allows us to trace the evolution of the disease, and to assess the correlation between the course of pathological process and the type of disease onset, age, sex, degree of activity and other factors, which contribute to the use of more exact methods for early detection of the adverse health consequences of JIA and the correct treatment. The purpose of the research was an improvement of the prognostic criteria for JIA by the retrospective chart review in patients with disease duration 1 year and 5–7–10 years. Materials and methods. The study included 47 children with joints form of JIA aged from 2 to 18 years. For diagnosis, clinical examination, standard laboratory and instrumental tests were used. A regression analysis was used for the determination of prognostic criteria, the informative value of the features and the predictive factors for each of criteria. Results. It was established that for prediction of the further 5–7-year course of JIA, the patient’s gender, inflammation of small joints of the hands, the presence of the rheumatoid factor (RF) played an essential role; and for 10-year and longer prognosis — the presence of eye lesions, the number of both affected and active joints were important. The significance of the following parameters has increased in prognostic model: the presence of RF, the duration of morning stiffness, radiological stage of the disease, laboratory indicators, such as erythrocyte sedimentation rate, level of C-reactive protein. For the 10-year prognosis of JIA, the effectiveness of treatment with methotrexate on initial stage was beneficial. These models determine variants of long-term course of JIA and include remission (up to 2 points), stabilization of the pathological process (from 2 to 3 points), which are assessed as favorable signs; and repeated exacerbations of the pathological process without progression of destructive changes in joints (from 3 to 4 points), clinical progression of disease, including radiological changes and joint destruction (more than 4 points), is classified as an unfavorable. Conclusions. The given methods for predicting the course of the JIA should be used at the initial stages of disease, it will allow to determine the real risk of adverse effects at early stage of pathological process and make it possible to choose adequate treatment.

To characterize and compare trends in body mass index (BMI) and variability in BMI between subjects with rheumatoid arthritis (RA) and matched non-RA subjects and to determine predictors of BMI trends and variability within RA subjects. This retrospective population-based cohort study included 1114 Olmsted County, Minnesota residents, 558 with incident RA (age $$\ge$$ 18 years, 1987 ACR criteria met in 1995–2009) and 556 non-RA subjects from the same underlying population with similar age, sex, and index calendar year. All subjects were followed until death, migration, or 12/31/2018. Generalized linear models with smoothing splines and random effects to account for multiple measurements per subject were used to examine trends in BMI measurements over time. Mean BMI of patients with incident RA (28.8 kg/m2) was not significantly different from that of non-RA subjects (28.9 kg/m2). There was no significant difference in BMI trends over time between RA and non-RA cohorts, or between seropositive for rheumatoid factor (RF) and/or citrullinated antibody (CCP-antibody) and seronegative RA patients, or between male and female subjects. RA subjects were noted to have significantly higher BMI variability following diagnosis compared to non-RA subjects [difference in standard deviation between RA and non-RA subjects prior to index (p = 0.12), 0–5 years after index (p = 0.044), and 5–15 years after index (p = 0.013)]. The BMI trajectory of the RA population is not significantly different compared to that of the non-RA population, but patients with RA demonstrate higher variability in BMI following diagnosis compared to the non-RA population.

While previous rheumatoid arthritis (RA) studies have focussed on cardiometabolic and lifestyle factors, less research has focussed on psychological variables including mood and cognitive health, and sleep. Cross-sectional analyses tested for associations between RA and RF+ (positive rheumatoid factor) vs. mental health (depression, anxiety, neuroticism), sleep variables and cognition scores in UK Biobank (total n = 484,064). Those RF+ were more likely to report longer sleep duration (β = 0.01, SE = 0.004, p β = 0.05, SE = 0.01, p β = 0.02, SE = 0.008, p β = − 0.03, SE = 0.01, p

Objective To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. Methods Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019–01 to 2021–12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. Results A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001–1.002, P P = 0.022), advanced age (OR = 1.080, 95% CI = 1.050–1.112, P P = 0.018) were independent risk factors for the existence of cardiovascular disease in patients. The combined coefficient calculated on the basis of the TyG index and rheumatoid factor was used to plot the receiver operating characteristic curve with an area under the curve of 0.791, which can be used to predict the potential risk of cardiovascular disease in patients with rheumatoid arthritis. Further sensitivity analysis found that the marker of focus remained associated with cardiovascular disease risk in a high-physical activity population with rheumatoid arthritis. The final trend test found a linear trend between the TyG index, rheumatoid factor levels and the risk of cardiovascular disease. Conclusion In the rheumatoid arthritis population, the TyG index and rheumatoid factor have some potential predictive value in determining the risk of cardiovascular disease, and the predictive efficacy is better when the two tests are combined.

Association between exposure to periodontal bacteria and development of autoantibodies related to rheumatoid arthritis (RA) has been widely accepted; however, direct causal relationship between periodontal bacteria and rheumatoid factor (RF) is currently not fully understood. We investigated whether periodontal bacteria could affect RF status. Patients with preclinical, new-onset, or chronic RA underwent periodontal examination, and investigation of subgingival microbiome via 16S rRNA sequencing. Degree of arthritis and RF induction was examined in collagen-induced arthritis (CIA) mice that were orally inoculated with different periodontal bacteria species. Subsequently, single-cell RNA sequencing analysis of the mouse spleen cells was performed. Patients with preclinical RA showed an increased abundance of the Porphyromonadacae family in the subgingival microbiome compared to those with new-onset or chronic RA, despite comparable periodontitis severity among them. Notably, a distinct subgingival microbial community was found between patients with high-positive RF and those with negative or low-positive RF (p=0.022). Oral infections with the periodontal pathogensP. gingivalisandTreponema denticolain CIA mice similarly enhanced arthritis score, but resulted in different levels of RF induction. Genes related to B cell receptor signaling, B cell proliferation, activation, and differentiation, and CD4+T cell costimulation and cytokine production were involved in the differential induction of RF in mice exposed to different bacteria. In summary, periodontal microbiome might shape RF status by affecting the humoral immune response during RA pathogenesis.

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation due to autoantibodies targeting multiple self-proteins. Most patients with poor prognosis show elevated titers of IgM antibodies specifically binding to IgG. Such autoreactive antibodies are referred to as rheumatoid factor (RF). However, their biological function and contribution to disease progression remains elusive. We have recently shown that autoreactive antibodies are present in healthy individuals and play an important role in regulating physiological processes. This regulatory mechanism is determined by the class and affinity of the autoreactive antibody, as low-affinity autoreactive IgM neutralizes the recognized autoantigen while high-affinity IgM protects its autoantigen from degradation. Here, we show that RFs possessing a high affinity and mono-specificity to IgG have a stabilizing effect on IgG, whereas low-affinity polyreactive RFs neutralize IgGin vivo. These results suggest that autoreactive IgM antibodies recognizing IgG play a crucial role in regulating IgG homeostasis and that a disbalance between IgM-mediated IgG degradation and stabilization might affect the onset and progression of autoimmune diseases. Consequently, restoring this balance using low-affinity anti-IgG IgM might be a promising therapeutic approach for autoimmune diseases involving autoreactive IgG.

Antibody-based assays are commonly used in clinical laboratories for analyzing plasma, serum and other samples for particular protein markers. Although such assays have been traditionally based on antibodies raised in mammals (e.g., mice, rabbits, goats), there are several advantages of using avian antibodies (IgY) raised in chickens, including production volumes, costs, and ethical/animal welfare considerations. A further disadvantage of using mammalian IgG in such assays is the potential for agglutination when exposed to rheumatoid factor (RF) in serum. However, when used in the free form the immune complexes formed with avian antibodies have been reported to have less ability than those formed with mammalian antibodies to cause the light scatter which are used for instrument measurement. In addition, when the amount of antigen exceeds the maximum precipitating point in relation to the amount of antibody, there is a rapid decline in the absorbance values of the immune complexes (antigen excess) when IgY is used. However, when avian antibodies are conjugated to a substrate and used in particle enhanced turbidimetric assays (PETIA), these problems are avoided. Here we investigated three clinical assays using chicken antibodies, one using free (unbound) IgY and two with IgY-based PETIA. The IgY PETIA demonstrated a strong scatter response, even at high antigen concentrations in contrast to the steep decline seen with free IgY antibodies. IgY PETIA reagents can provide test results with low coefficient of variation (