Country-level socioeconomic status relates geographical latitude to the onset of RA: a worldwide cross-sectional analysis in the METEOR registry.

OBJECTIVE: Age at rheumatoid arthritis (RA) onset varies by geographical latitude. We have investigated to what extent differences in patient-specific factors and country-level socioeconomic indicators explain this variability. METHODS: Patients with RA from the worldwide METEOR registry were included. Bayesian multilevel structural equation models were used to study the relationship between the absolute value of (hospital) geographical latitude and age at diagnosis (as a proxy for age at RA onset). We examined to what extent this effect is mediated by individual patient characteristics and by country-specific socioeconomic indicators and disentangled whether the observed effects occurred at the patient, hospital, or country levels. RESULTS: We included 37 981 patients from 93 hospitals in 17 geographically widespread countries. Mean age at diagnosis per country ranged from 39 (Iran) to 55 (Netherlands) years. Per degree increase in country latitude (between 9.9° and 55.8°), mean age at diagnosis increased by 0.23 years (95% credibility interval: 0.095 to 0.38) (reflecting >10 years difference in age at RA onset). For hospitals within a country, this latitude effect was negligible. Inclusion of patient-specific factors (eg, gender, anticitrullinated protein antibodies status) in the model augmented the main effect from 0.23 to 0.36 years. Inclusion of country-level socioeconomic indicators (eg, gross domestic product per capita) in the model almost effaced the main effect (from 0.23 to 0.051 (-0.37 to 0.38)). CONCLUSIONS: Patients living closer to the equator get RA at a younger age. This latitude gradient was not explained by individual patient characteristics, but rather by countries' socioeconomic status, providing a direct link between countries' level of welfare and the clinical onset of RA.

How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies.

OBJECTIVES: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication. METHODS: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS. RESULTS: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95% CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1 year of follow-up. CONCLUSIONS: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.

Tobacco-Derived Lipopolysaccharide, Not Microbial Translocation, as a Potential Contributor to the Pathogenesis of Rheumatoid Arthritis.

Microbial lipopolysaccharides (LPS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), possibly driving a systemic inflammatory response that may trigger the development and/or exacerbation of the disease. To explore the existence of this mechanism in African RA patients, we have measured systemic levels of LPS and its surrogate, LPS-binding protein (LBP), as well as those of intestinal fatty acid-binding protein (I-FABP), pulmonary surfactant protein D (SP-D), and cotinine in serum to identify possible origins of LPS, as well as associations of these biomarkers with rheumatoid factor (RF) and anticitrullinated peptide (aCCP) autoantibodies and the DAS 28-3 clinical disease severity score. A cohort of 40 disease-modifying antirheumatic drug-naïve, black South African RA patients rated by compound disease scores and 20 healthy subjects and 10 patients with chronic obstructive pulmonary disease (COPD) as controls were included in this study. Levels of the various biomarkers and autoantibodies were measured using a combination of ELISA and immunofluorimetric and immunoturbidometric procedures. LPS levels were lowest in the RA group compared to the healthy controls (p = 0.026) and COPD patients (p = 0.017), while LBP levels were also significantly lower in RA compared to the healthy individuals (p = 0.036). Levels of I-FABP and SP-D were comparable between all three groups. Categorisation of RA patients according to tobacco usage revealed the following significant positive correlations: LBP with C-reactive protein (p = 0.0137); a trend (p = 0.073) towards an association of LBP with the DAS 28-3 disease severity score; RF-IgG antibodies with both LPS and LBP (p = 0.033 and p = 0.041, respectively); aCCP-IgG antibodies with LPS (p = 0.044); and aCCP-IgG with RF-IgM autoantibodies (p = 0.0016). The findings of this study, several of them novel, imply that tobacco products, as opposed to microbial translocation, represent a potential source of LPS in this study cohort of RA patients, again underscoring the risks posed by tobacco usage for the development and severity of RA.

Probable endometrial tuberculosis in a patient with rhupus.

Endometrial tuberculosis (TB) is an uncommon manifestation of disseminated TB. Rhupus is the coexistence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We describe a case of endometrial TB in rhupus patient an immunosuppressed. Contribution: We describe an uncommon presentation of disseminated TB, endometrial TB, in a rare rheumatic disease, rhupus. A high index of suspicion for TB is imperative in immunocompromised patients presenting with chronic urogenital symptoms especially in an endemic area.

Osteoporosis in Black South Africans With Rheumatoid Arthritis.

Background Osteoporosis is a common comorbidity associated with rheumatoid arthritis (RA). The aim of this study was to determine the risk factors and possible predictors of osteoporosis in black patients with RA. Methods A retrospective study of 120 randomly selected RA patients attending an arthritis clinic in Johannesburg, South Africa, was carried out, in which 60 patients were with and 60 without osteoporosis. The demographics, disease activity, American College of Rheumatology (ACR) functional status, treatment, and dual-energy X-ray absorptiometry (DEXA) characteristics were compared. Statistical analysis was performed using SPSS version 25.0 (IBM Corp, Armonk, NY). Bivariate comparisons of demographic factors, disease factors, and T-scores between patients with and without osteoporosis were performed, using two-sided t-tests for continuous variables and chi-squared tests for categorical variables. Possible predictors of osteoporosis were subsequently entered into a multivariate logistic regression model with osteoporosis being the dependent variable. The level of significance for all analyses was set at p < 0.05. Results The median (IQR) age of the overall cohort was 67 (61.0, 72.8) years, the majority (95.5%) were female, of which 97.4% were postmenopausal. The mean disease duration from diagnosis to the DEXA was 8.6 ± 6.2 years. Rheumatoid factor (RF) positivity was 89.2% and anti-cyclic citrullinated peptide (ACCP) positivity was 82.7%. The median (IQR) for disease activity score 28 swollen and tender joint count using the erythrocyte sedimentation rate (DAS-28 ESR) was 3.4 (2.8-4.7) and the median (IQR) for ESR was 41 (22, 64.3) mm/h. There were significantly more patients treated with triple therapy in the no osteoporosis group, 38 (63.3%), than in the osteoporosis group, 21 (35%) (p = 0.00). The ACR functional class was significantly worse in the RA patients with osteoporosis than in the RA patients without osteoporosis [median (IQR), 2 (2, 3) vs 2 (1, 2), (p = 0.03)], respectively. Conclusion This study found that a worse ACR functional class was significantly associated with osteoporosis. In addition, the use of triple therapy had a protective effect. Early recognition of the risk factors for osteoporosis should be sought, with prompt preventative measures, screening, and treatment.