Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Cancer risks in patients with ankylosing spondylitis and the effects of biologic agents: a population-based study.

OBJECTIVES: To conduct a population-based analysis of the malignancy risks of patients with ankylosing spondylitis (AS). METHODS: A total of 1,796 patients with AS and 7,184 age- and sex-matched controls (1:4 ratio) were selected from the Korea National Health Insurance Service-National Sample Cohort database. Data of patients diagnosed with AS (code M45) according to the International Classification of Diseases (ICD) 10th edition, between 2002 and 2019, were reviewed. These data were extracted based on the ICD codes assigned to cancer patients. RESULTS: Cancer developed in 168/1,796 patients (9.3%) after the AS diagnosis. After adjusting for confounders, the cancer risk of patients with AS was not significantly increased compared with that of controls (adjusted hazard ratio [HR]: 1.1; 95% confidence interval [CI]: 0.93-1.31). However, the risks for upper gastrointestinal (GI) cancer (adjusted HR: 1.51; 95% CI: 1.07-2.12) and haematologic malignancy (adjusted HR: 2.36; 95% CI: 1.2-4.65) were significantly higher in patients with AS than in controls. There were no significant differences in the risks for other major cancers between patients with AS and controls. Regarding medication for AS, the HR of upper GI cancer was higher in patients with AS compared with controls (adjusted HR: 1.51; 95% CI: 1.00-2.29). CONCLUSION: The overall cancer risks in patients with AS were not significantly different compared with the controls. However, while the effect of non-steroidal anti-inflammatory drugs on upper GI cancer cannot be ruled out, patients with AS exhibited a significant increase in the risk of both upper GI cancer and hematologic malignancy.

Systemic sclerosis and risk of bronchiectasis: a nationwide longitudinal cohort study.

BACKGROUND: The association between systemic sclerosis and the development of bronchiectasis is unclear. This study aimed to compare the risk of bronchiectasis between individuals with systemic sclerosis and those without using a nationwide longitudinal dataset. METHODS: Using the Korean National Health Insurance Service dataset between 2010 and 2017, we identified 4845 individuals aged ≥ 20 years with systemic sclerosis and 24,225 without systemic sclerosis who were matched 1:5 by age and sex. They were followed up until the date of a bronchiectasis diagnosis, death, or December 31, 2019, whichever came first. RESULTS: During a median follow-up period of 6.0 (interquartile range, 3.2-8.7) years, 5.3% of the systemic sclerosis cohort and 1.9% of the matched cohort developed bronchiectasis, with incidence rates of 9.99 and 3.23 per 1000 person-years, respectively. Even after adjusting for potential confounders, the risk of incident bronchiectasis was significantly higher in the systemic sclerosis cohort than in the matched cohort (adjusted hazard ratio 2.63, 95% confidence interval 2.22-3.12). A subgroup analysis of individuals with systemic sclerosis revealed that the risk of incident bronchiectasis was notably higher in younger individuals aged 20-39 years (P for interaction = 0.048) and in those without other coexisting connective tissue diseases (P for interaction = 0.006) than in their counterparts. CONCLUSIONS: The risk of incident bronchiectasis is higher in individuals with systemic sclerosis than those without. Bronchiectasis should be considered one of the pulmonary manifestations related to systemic sclerosis.

Clinicopathological Characteristics of Autoimmune-Like Hepatitis Induced by COVID-19 mRNA Vaccine (Pfizer-BioNTech, BNT162b2): A Case Report and Literature Review.

Widespread use of vaccinations worldwide in the coronavirus disease (COVID-19) pandemic has resulted in various side effects. Here, we presented a 27-year-old man with autoimmune-like hepatitis after the first dose of the BNT162b2 (mRNA) COVID-19 vaccine and reviewed previous reports. He presented with sweating, febrile sensations, and general weakness. He did not have any medical histories. Although he was treated with biphenyl dimethyl dicarboxylate and ursodeoxycholic acid, the elevated liver enzyme levels persisted for 2 months. Liver biopsy demonstrated portal inflammation with rosette formation, interface hepatitis, and infiltration of lymphocytes, histiocytes, plasma cells, and eosinophils. Especially, centrilobular edema and necrosis were found. The symptoms and liver enzymes improved with prednisolone treatment. If persistently elevated liver enzymes are found after COVID-19 mRNA vaccination, the possibility of autoimmune-like hepatitis induced by the vaccine should be considered and a careful pathologic evaluation is required.

Association between SYVN1 and SEL1 genetic polymorphisms and remission in rheumatoid arthritis patients treated with TNF-α inhibitors: a machine learning approach.

Rheumatoid arthritis (RA) is a severe chronic inflammatory condition that affects joint synovium. Suppressor/enhancer of lin-12-like (SEL1L)-Synoviolin 1 (SYVN1)-mediated endoplasmic reticulum-associated degradation (ERAD) is highly associated with RA development. Although targeting SEL1L-SYVN1-mediated ERAD can be beneficial, studies that evaluate the association between polymorphisms in their genes and remission from the disease in RA patients taking tumor necrosis factor (TNF)-α inhibitors have yet to be carried out. Hence, the purpose of this study was to investigate the association between SYVN1 and SEL1L polymorphisms and TNF-α inhibitor response using various machine learning models. A total of 12 single-nucleotide polymorphisms (SNPs), including 5 SNPs in SYVN1 and 7 SNPs of SEL1L were investigated. Logistic regression analysis was used to examine the relationship between genetic polymorphisms and response to treatment. Various machine learning methods were employed to evaluate factors associated with remission in patients receiving TNF-α inhibitors. After adjusting for covariates, we found that sulfasalazine and rs2025214 in SEL1L increase the remission rates by approximately 3.3 and 2.8 times, respectively (95% confidence intervals 1.126-9.695 and 1.074-7.358, respectively). Machine learning approaches showed acceptable prediction estimates for remission in RA patients receiving TNF-α inhibitors, with the area under the receiver-operating curve (AUROC) values ranging from 0.60 to 0.65. A polymorphism of the SEL1L gene (rs2025214) and sulfasalazine were found to be associated with treatment response in RA patients receiving TNF-α inhibitors. These preliminary data could be used to tailor treatment for RA patients using TNF-α inhibitors.

Clinicopathological Characteristics of Inflammatory Myositis Induced by COVID-19 Vaccine (Pfizer-BioNTech BNT162b2): A Case Report.

As more individuals were coronavirus disease 2019 (COVID-19) vaccinated, unexpected side effects appeared. Herein, we present the case of a 30-year-old man with myopathy in both extremities after the second dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Symptoms, swelling and pain, started from the proximal upper and lower extremities and extended to the distal parts. Although he underwent massive hydration, the muscle enzyme level continuously increased. He complained of dysphagia and dysarthria. Microscopically, muscle biopsy showed multifocal or scattered macrophage infiltration and degenerated myofibers. In contrast to general myopathy including inflammatory myositis and rhabdomyolysis, vaccine-induced inflammatory myositis shows a prolonged increase in muscle enzyme levels and multifocal macrophage infiltration with necrosis of the muscle fibers. Symptoms improved with glucocorticoid and immunosuppressive treatment. If vaccinated individuals experience severe and continuous muscle pain and swelling, clinicians should consider vaccine-induced inflammatory myositis, measure the muscle enzyme levels, and perform muscle biopsy for a definite diagnosis.

Clinical Association between Gout and Parkinson's Disease: A Nationwide Population-Based Cohort Study in Korea.

Background and Objectives: This retrospective cohort study aimed to investigate the association between gout and Parkinson's disease (PD) in Korea. Materials and Methods: Overall, 327,160 patients with gout and 327,160 age- and sex-matched controls were selected from the Korean National Health Insurance Service (NHIS) database. PD incidence was evaluated by reviewing NHIS records during the period from 2002 to 2019. Patients with a diagnosis of gout (International Classification of Diseases-10 (ICD-10), M10) who were prescribed medications for gout, including colchicine, allopurinol, febuxostat, and benzbromarone for at least 90 days were selected. Patients with PD who were assigned a diagnosis code (ICD-G20) and were registered in the rare incurable diseases (RID) system were extracted. Results: During follow-up, 912 patients with gout and 929 control participants developed PD. The incidence rate (IR) of overall PD (per 1000 person-years) was not significantly different between both groups (0.35 vs. 0.36 in gout and control groups, respectively). The incidence rate ratio (IRR) was 0.98 (95% CI: 0.89-1.07). The cumulative incidence of PD was not significantly different between the groups. No association between gout and PD was identified in univariate analysis (HR = 1.00, 95% CI: 0.91-1.10, p = 0.935). HR increased significantly with old age (HR = 92.08, 198, and 235.2 for 60-69 years, 70-79 years, and over 80 years, respectively), female sex (HR = 1.21, 95% CI: 1.07-1.37, p = 0.002), stroke (HR = 1.95, 95% CI: 1.76-2.16, p < 0.001), and hypertension (HR = 1.16, 95% CI: 1.01-1.34, p = 0.04). Dyslipidemia exhibited an inverse result for PD (HR = 0.6, 95% CI: 0.52-0.68, p < 0.001). Conclusions: This population-based study did not identify an association between gout and PD. Age, female sex, stroke, and hypertension were identified as independent risk factors for PD, and dyslipidemia demonstrated an inverse result for PD.

Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis.

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p < 0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p = 0.001) and IL-6 (p < 0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p = 0.007) and TNF-α (p = 0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p = 0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p = 0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.