Methotrexate-induced manic episode in a patient with seropositive rheumatoid arthritis: A case report

BackgroundPatients with seropositive rheumatoid arthritis (RA) (positive Rheumatoid Factor (RF)) are more susceptible to extra-articular manifestations [1]. The role of RF in the occurrence of comorbidity is not clear.ObjectivesWe aimed...

The hand and wrist are among the most common anatomical areas involved in rheumatic diseases, especially seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The purpose of this study was to identify the most differentiating radiographic characteristics of PsA, seropositive RA, and seronegative RA, particularly in the early stages. A retrospective analysis of radiographic hand findings was performed on 180 seropositive RA patients (29 males, 151 females, mean age at the point of acquisition of the analyzed radiograph of 53.4 y/o, SD 12.6), 154 PsA patients (45 males, 109 females, age median of 48.1 y/o, SD 12.4), and 36 seronegative RA patients (4 males, 32 females, age median of 53.1 y/o, SD 17.1) acquired during the period 2005–2020. Posterior–anterior and Nørgaard views were analyzed in all patients. The radiographs were evaluated for three radiographic findings: type of symmetry (asymmetric/bilateral/changes in corresponding joint compartments/‘mirror-image’ symmetry), anatomic location (e.g., wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) joints), and type of lesions (e.g., juxta-articular osteoporosis, bone cysts, erosions, proliferative bone changes). The study showed that symmetric distribution of lesions defined as ‘lesions present in corresponding compartments’ was more suggestive of seropositive or seronegative RA than PsA. Lesions affecting the PIP joints, wrist, or styloid process of the radius; juxta-articular osteoporosis, joint space narrowing, joint subluxations, or dislocations were more common in patients with seropositive RA than in those with PsA, whereas DIP joints’ involvement and proliferative bone changes were more likely to suggest PsA than seropositive RA. Lesions in PIP, MCP, and wrist joints, as well as erosions, advanced bone damage, joint subluxations, dislocations, and joint space narrowing, were more common in seropositive RA patients than in seronegative RA patients. The ulnar styloid was more commonly affected in seronegative RA patients than in PsA patients. The study confirmed that types of bone lesions and their distribution in the hands and wrists can be useful in differentiating seropositive RA from PsA and suggests that seronegative RA varies in radiological presentation from seropositive RA and PsA.

BackgroundPrevalence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (ACPA) positivity in US patients with rheumatoid arthritis (RA) is around 70% [1]. Seropositive RA status, defined by positivity for...

Background:The excess mortality in rheumatoid arthritis (RA) has been known for decades and persists in recent literature. However, the mortality trend in seropositive and seronegative RA has not yet been...

Objective. To determine the features of the radiation criteria of chronic generalized periodontitis in rheumatoid arthritis (RA).Materials and Methods. 71 patients were examined with chronic generalized periodontitis and rheumatoid arthritis. The average age of patients was 48 ± 6.9 years. All patients underwent cone beam computed tomography (CBCT) (n = 71), orthopantomography (n = 42).Results. In the group of patients with seronegative RA, radiation criteria according to CBCT were more pronounced in comparison with patients with seropositive RA. Signs of a decrease in bone density according to CBCT correlated with changes in the musculoskeletal system in 68.9 % of cases in the group with seropositive RA (r = 0.954). When analyzing CBCT in assessing jaw density for patients with RA, it was found that the method is effective. In case of seropositive or seronegative RA, the lowest bone density according to CBCT is found in the structure of the upper jaw.Conclusion. 1. In the group of patients with seronegative RA, radiation criteria according to CBCT were more pronounced compared with patients with seropositive RA (p < 0.05). 2. A decrease in bone density according to CBCT correlated with changes in the musculoskeletal system in the group with seropositive RA (r = 0.954). 3. When analyzing CBCT in assessing jaw bone density for patients with RA, it was found that the method is effective (AUROC 0.993, CI 0.958 – 0.996). 4. It was found that in patients with chronic generalized periodontitis on the background of seropositive or seronegative RA, the lowest bone density according to CBCT is found in the structure of the upper jaw.

Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden

To evaluate clinical prognosis following the introduction of a first targeted therapy (TT) according to the serological profile of rheumatoid arthritis (RA) and to analyze differences in efficacy of TT. This single-center retrospective study included patients with RA who received a first TT between 2000 and 2020. Patients were seropositive (IgM and/or IgA rheumatoid factors plus anti-CCP) or seronegative (without autoantibodies). Various data were collected at baseline and during follow-up. The primary endpoint was remission (assessed by DAS28) at one and two years. Among 259 patients, 164 (63.3%) were seropositive and presented higher disease activity and more frequent erosive involvement than seronegative patients at TT introduction. The most prescribed first TTs were etanercept for seronegative RA (47 ([49.5%) versus 41 (25%), p < 0.001) and abatacept for seropositive RA (41 (25%) versus 6 (6.3%), p < 0.001). Remission rates and TT switches were not significantly different between groups. Initial DAS28-CRP and number of painful joints were independent prognostic factors associated with absence of remission at one year (OR 0.46 (0.26, 0.80), p = 0.007) and two years (OR 0.90 (0.82, 0.98), p = 0.027) respectively. Among seropositive patients, the two-year remission rate was not significantly different according to the therapeutic class received (cellular- versus cytokine-targeted). Patients with seropositive RA showed more active and severe disease than patients with seronegative RA at the introduction of a first TT. Although the choice of the first TT varied according to serological profile and time of analysis, clinical prognosis at one and two years was similar between groups. Key Points • Seropositive versus seronegative RA was more active at start of first targeted therapy. • First-line TTs were etanercept for seronegative RA and abatacept for seropositive RA. • Rate of targeted therapy switches was comparable between both groups. • Remission rates at 1 and 2years were similar in seropositive and seronegative RA. • Remission rates were similar for cellular and cytokine inhibitors in seropositive RA.

Toll-like receptors (TLRs) are known to have an important role in triggering the innate immune response and in priming antigen-specific adaptive immunity and inflammation. The differences in synovial tissue expression of the TLRs between seronegative and seropositive rheumatoid arthritis (RA) were examined from 9 seropositive RA, 5 seronegative RA and 4 osteoarthritis (OA) patients. Synovitis status was assessed using Krenn’s scoring and TLR 1–9 expression by immunohistochemistry. Tissue citrulline content was analysed by HPLC method. In RA TLR expression was generally higher than in OA. TLR2 expression was higher in both seronegative and seropositive RA compared to OA. TLR 1, 4 and 8 expressions were higher in seropositive RA than in seronegative RA or in OA. For TLRs 3, 5, 6, 7 and 9 local differences of expression were found between groups. TLR 1–9 expression correlated with the synovitis grade. No statistical difference was found in synovial tissue citrulline content between the groups. In seropositive RA, the TLR repertoire in the synovial tissue differs from seronegative RA and could explain differences in disease outcomes. The high expression of protein sensing (TLR1, TLR2 and TLR4) and nucleic acid sensing TLRs (TLR7, TLR8 and TLR9) in the seropositive RA could make the synovium primed for reacting to citrullinated proteins and nucleic acids that could be released to extracellular space in formation of neutrophil extracellular traps. This reactivity could be augmented by Fc receptor activation by anti-citrullinated protein antibody immunocomplexes associated with seropositive RA.

The temporal mortality trend in seropositive and seronegative rheumatoid arthritis: a Danish population-based cohort study.

Objectives: To determine the differences in a proliferation-inducing ligand (APRIL) between seropositive and seronegative rheumatoid arthritis (RA) patients and further investigate the possible pathogenesis of the two subtypes of RA.Method:Concentrations of APRIL in sera (18 seropositive RA patients, 16 seronegative RA patients, and 10 healthy controls) and synovial fluid (SF) (eight seropositive RA patients, two seronegative RA patients, and 10 controls) were detected by enzyme-linked immunosorbent assay (ELISA). Infiltration of plasma cells, macrophages, and APRIL-positive cells in the synovium [14 seropositives, eight seronegatives, and 10 osteoarthritis (OA) controls] was detected by immunohistochemistry. Correlations between serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), and sera/SF levels of APRIL and synovial cell infiltration were analysed.Results: The mean serum APRIL level of seropositive RA patients was significantly higher than that of seronegative patients (26.1 ± 31.2 vs. 8.0 ± 10.2 ng/mL, p = 0.03). The level of APRIL in the SF of seropositive RA patients was comparable to that of seronegative patients [47.9 ± 54.4 vs. 32.82 (6.52–59.12) ng/mL, p > 0.05]. The SF APRIL level of RA patients was higher than that of patients with other inflammatory arthritis. Dramatically increased infiltration of APRIL-positive cells in the RA synovium was observed compared with the OA group (seropositive RA vs. OA, p < 0.001; seronegative RA vs. OA, p = 0.001). The infiltration of both plasma cells and macrophages was more in seropositive RA than in OA (p = 0.013 and p = 0.003, respectively).Conclusions: The serum APRIL levels of seropositive RA patients are significantly higher than those of seronegative RA patients. APRIL may participate in the formation of seropositive RA.

Background:Several studies show increased risk of dementia among individuals with rheumatoid arthritis (RA), while others show no association. One reason for this discrepancy might be differential association by serostatus. No...

SAT0596 RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS AMONG PATIENTS WITH RHEUMATOID ARTHRITIS AND A LOW-INTERMEDIATE Á PRIORI RISK OF CORONARY ARTERY DISEASE AFTER INITIAL CT-BASED DIAGNOSIS AND TREATMENT A REGISTRY-BASED FOLLOW-UP STUDY USING DATA FROM THE WESTERN DENMARK HEART REGISTRY

Does Rheumatoid Arthritis Increase the Risk of COPD?: A Nationwide Retrospective Cohort Study

The numbers of pokeweed mitogen (PWM)-induced IgM-, IgG- and IgA-secreting cells (SC) in mononuclear cell cultures from patients with seropositive and seronegative rheumatoid arthritis (RA) were reduced compared to those of control persons. Significant numbers of IgM rheumatoid factor (RF)-SC were only found in PWM-induced cultures from patients with seropositive RA (median: 7 IgM RF-SC/10(6) and controls greater than or equal to 50 years (median: 6 IgM RF-SC/10(6). The ratio of IgM RF-SC to total IgM-SC (RF/IgM-SC ratio) was significantly higher in patients with seropositive RA (median: 0.6%) than in controls greater than or equal to 50 years (median: 0.1%). Patients with seropositive RA and RF/IgM-SC ratios above 0.5% had higher Waaler-Rose titers than those with ratios under 0.5%. Our results indicate that secretion of Ig by PWM-induced blood lymphocytes is suppressed in patients with RA compared to controls; in seropositive RA a higher fraction of in vitro activated IgM-SC secrete IgM RF as compared to controls and patients with seronegative RA.

To compare the frequencies and responsiveness of rheumatoid factor (RF)-producing B cells in the peripheral blood of patients with seronegative and seropositive rheumatoid arthritis (RA). Frequencies of IgM+, IgG+, and RF+ B cells were determined by limiting-dilution analysis of purified peripheral blood B cells from 6 patients with seropositive RA, 8 patients with seronegative RA, and 7 normal controls. B cell help was provided by cloned T helper cells, which were stimulated by either anti-CD3 or the bacterial superantigen staphylococcal enterotoxin D (SED). IgM and IgG antibodies and RF in culture supernatants were detected by enzyme-linked immunosorbent assay. In the presence of anti-CD3-stimulated T helper cells, 2-10% of B cells from normal individuals secreted IgM and IgG antibodies. The frequency of RF+ B cells was low and ranged from 1:182 to 1:885 (RF+: IgM+) B cells. In patients with seropositive RA, the numbers of Ig-producing B cells were reduced by a factor of 2, while the fraction of RF+ B cell precursors was expanded by more than 50-fold (7-20% of IgM+ B cells; P = 0.004). Patients with seronegative RA had higher frequencies of RF-producing B cells (1.5-6% of IgM+ B cells) than normal individuals (P = 0.002), but not to the same extent as seropositive patients (P = 0.002). Stimulation of B cells using SED preferentially induced RF+ B cells in normal controls and in patients with seronegative and seropositive RA. B cell precursors with the potential to secrete RF were detectable in high frequencies in normal individuals and in patients with seropositive and seronegative RA. In all donors, these B cells could be stimulated with the bacterial superantigen SED. In normal individuals, RF+ B cells remained nonresponsive to help provided by anti-CD3-activated T cells, but were responsive in RA patients. Seronegative and seropositive RA form a continuous spectrum of disease, with a higher number of RF-secreting B cells in the seropositive patients.