Objective: To estimate and compare the burdens of opportunistic infections and herpes zoster in real-world practice among patients with various systemic rheumatic diseases. Methods: This 13-year cohort study used national health insurance data to compare the incidence rates (IRs) of nine opportunistic infections among patients with five rheumatic diseases. The analyses were stratified according to follow-up duration using Poisson regression, and Cox models were used to compare the risk of first opportunistic infection. Results: During 2000–2013, we identified 76,966 patients who had polymyositis/dermatomyositis (PM/DM, 2270 cases), systemic lupus erythematosus (SLE, 15,961 cases), systemic sclerosis (SSc, 2071 cases), rheumatoid arthritis (RA, 38,355 cases), or primary Sjögren’s syndrome (pSS, 18,309 cases). The IR of opportunistic infections was highest for PM/DM cases (61.3/1000 person-years, 95% confidence interval [CI] 56.6–66.2), followed by SLE cases (43.1/1000 person-years, 95% CI 41.7–44.5), SSc cases (31.6/1000 person-years, 95% CI 28.3–35.1), RA cases (25.0/1000 person-years, 95% CI 24.4–25.7), and pSS cases (24.1/1000 person-years, 95% CI 23.1–25.2). Multivariable Cox analysis revealed that, relative to SLE, PM/DM was associated with a significantly higher risk of opportunistic infections (hazard ratio 1.18, 95% CI 1.08–1.29). The risk of opportunistic infections was highest during the first year after the diagnosis of all five rheumatic diseases. Conclusions: The risk of opportunistic infection was highest for PM/DM, followed by SLE, SSc, RA, and pSS. Careful observation and preventive therapy for opportunistic infections may be warranted in selected PM/DM patients, especially during the first year after the diagnosis.

Background: Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. Methods: We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. Results: None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients’ than in PSA patients’ stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group. Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation. The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.

Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

The long-term renal outcome in patients with primary Sjögren's syndrome (pSS) remains uncertain. We aimed to determine the absolute incidence and relative risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in patients with pSS at the general population level. We performed a retrospective cohort study using a national health insurance database in Taiwan from 2000 to 2013. We calculated the cumulative incidence of CKD and ESRD in our pSS and age-, sex- and entry time-matched control cohorts. Cox regression analyses were used to estimate adjusted hazard ratios (aHRs) after adjusting for comorbidities and medications. Among 17 505 patients with incident pSS, 1008 (5.8%) developed CKD and 38 (0.22%) developed ESRD. Of the 87 525 non-pSS controls, 3173 (3.6%) developed CKD and 256 (0.29%) developed ESRD. The risk of CKD was higher in patients with pSS than in the non-pSS controls (adjusted hazard ratio [HR] 1.49, 95% confidence interval [95% CI] 1.38-1.59). Notably, the risk of ESRD was similar in both pSS and non-pSS cohorts (aHR 0.82, 95% CI 0.58-1.16). Renal prognosis among patients with pSS and renal involvement is good. Although the risk of ESRD did not increase in patients with pSS, a significantly increased risk of CKD was observed in these patients, indicating the need for increased vigilance in regular monitoring for renal complications in patients with pSS.

Rheumatoid arthritis (RA) is associated with poor bone mineral density (BMD). We designed the current study owing to the lack of long-term prospective studies regarding whether a high disease activity leads to increased bone loss. We have continually enrolled patients with RA. According to the average disease activity score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) during follow-up, the patients were classified into remission, low disease activity, and moderate or high disease activity groups. Patients were examined with dual-energy X-ray absorptiometry at baseline and after 3 years of follow-up. BMD changes were compared among the groups. We have studied 477 patients. Overall BMD was significantly reduced from baseline to the 3-year follow-up (p < 0.05). After stratifying according to the time-averaged DAS28-ESR levels and use of anti-osteoporosis treatment (AOT), the BMD values of the femur and spine significantly increased in patients in the remission group with AOT. The BMD changes of different DAS28-ESR patients were further compared using the generalized estimation equation model. For the patients on AOT, the negative change in femoral BMD values of the moderate or high activity group was significant when compared with the remission group with positive BMD changes (regression coefficient, –0.038; 95% confidence interval, –0.055 to –0.021). For RA patients, if remission is achieved, AOT can better improve BMD, especially in the femur. In addition, moderate or high disease activity will lead to significant bone loss; therefore, disease activity must be actively controlled.