Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited. Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan’s National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs. A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8–12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9–86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30–36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes. Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE. Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections. Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens. Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

Objectives: RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. Methods: This retrospective nationwide study used the 2000–2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. Results: TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P < 0.001) and THR (7.09 vs 9.16/1000 person-years, P < 0.001). After adjustment for confounding factors, the regular bDMARD subgroup (average dose >0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. Conclusions: Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.

The risk of psoriasis in diabetic patients has rarely been explored. This study aims to compare the risk of incident psoriasis in patients with Type 2 diabetes (T2D) who initiate dipeptidyl peptidase‐4 inhibitors (DPP‐4is) or thiazolidinediones (TZDs) with those who initiate sulfonylureas, the most common second‐line glucose‐lowering therapy, in addition to metformin monotherapy. This sequential, propensity‐score‐matched, new‐user comparative effectiveness study utilized a target trial emulation framework. It included adults with T2D receiving metformin monotherapy, using data from 2006 to 2015 from a general population database in Taiwan. The primary outcome was the incidence of psoriasis, determined through diagnoses recorded in urgent care, hospital, and outpatient department records. Cox proportional hazards and Poisson regressions with 1:4 propensity score matching was employed to evaluate the risk factors for psoriasis after adjusting for comorbidities and the use of other medications. In 49,810 propensity score‐matched adults with T2D (27,630 men [55.4%]; mean age 57.5 years) identified in the database, the incidence rate of psoriasis in DPP‐4i users was 188 cases per 100,000 person‐years, lower than in sulfonylurea users (467 cases per 100,000 person‐years), with a hazard ratio(HR) of 0.422 (95% CI, 0.273–0.716). For the TZD vs. sulfonylurea comparison, the HR was 0.35, but the smaller matched dataset resulted in wide confidence intervals. The findings suggest that the use of DPP‐4is is associated with a lower risk of psoriasis compared to sulfonylureas in patients with T2D. These results can guide the selection of glucose‐lowering therapies in T2D patients who are at risk of developing psoriasis.

The aim of this study was to examine oxidative stress and low level of α-1-antitrypsin (A1AT) in primary Sjögren’s syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, α-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-liquid chromatography–tandem mass spectrometry (nano-LC-MS/MS) from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Our study suggests that elevated HNE-protein adduct, oxidative stress, level (odds ratio (OR) 4.877, p = 0.003), lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50–63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.