Difficult-to-treat rheumatoid arthritis (D2T RA) is a multifactorial condition in which disease activity of RA persists despite consecutive treatment with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). To evaluate the prevalence and predictive risk factors of D2T RA in our institution, a single-center, retrospective study was conducted. Medical records of RA patients, who visited our hospital from 2011 to 2020 and had a follow-up of more than 6 months, were retrospectively reviewed. D2T RA was defined as RA with a disease activity score of 28 - erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or higher at the last visit, despite the use of at least two b/tsDMARDs. A logistic regression model was used to identify risk factors. A total of 672 patients were enrolled. The mean age at disease onset was 52.1 years and females were dominant (76.3%). After a mean follow-up of 46.6 months, patients with D2T RA accounted for 7.9% of overall patients. Multivariate analysis identified high rheumatoid factor (RF) levels (≥156.4 IU/mL, odds ratio [OR]: 1.95), DAS28-ESR (OR: 1.24), and coexisting pulmonary disease (OR: 2.03) as predictive risk factors of D2T RA. In conclusion, high RF levels, high DAS28-ESR, and coexisting pulmonary disease at baseline can predict the development of D2T RA.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cell-to-cell contact or indirectly via humoral factors. Recently, growing evidence has revealed essential role of adipokines, which are multifunctional signal transduction molecules, in the immune system. In this review, we summarize the current understanding of the cross-talk between leptin, one of the most well-known and best-characterized adipokines, and osteoimmunology. Furthermore, we discuss the contribution of leptin to the pathogenesis of RA and its potential mechanisms.
Adaptive immunity plays central roles in the pathogenesis of rheumatoid arthritis (RA), as it is regarded as an autoimmune disease. Clinical investigations revealed infiltrations of B cells in the synovium, especially those with ectopic lymphoid neogenesis, associate with disease severity. While some B cells in the synovium differentiate into plasma cells producing autoantibodies such as anti-citrullinated protein antibody, others differentiate into effector B cells producing proinflammatory cytokines and expressing RANKL. Synovial B cells might also be important as antigen-presenting cells. Synovial T cells are implicated in the induction of antibody production as well as local inflammation. In the former, a recently identified CD4 T cell subset, peripheral helper T (Tph), which is characterized by the expression of PD-1 and production of CXCL13 and IL-21, is implicated, while the latter might be mediated by Th1-like CD4 T cell subsets that can produce multiple proinflammatory cytokines, including IFN-γ, TNF-α, and GM-CSF, and express cytotoxic molecules, such as perforin, granzymes and granulysin. CD8 T cells in the synovium are able to produce large amount of IFN-γ. However, the involvement of those lymphocytes in the pathogenesis of RA still awaits verification. Their antigen-specificity also needs to be clarified.
Western countries that were first to administer the COVID-19 vaccination report cases of vaccine-induced axillary lymphadenitis with high FDG uptake. However, no such findings have been reported from any Asian countries. We report here a confusing case of a 31-year-old female cancer survivor with high FDG uptake in her axillary lymph nodes, suggesting recurrence, following mRNA COVID-19 vaccination. Although the value of SUVmax was elevated (12.7), additional imaging revealed that her lymphatic lesions were benign, and they resolved spontaneously. This case of a strong immune reaction to COVID-19 vaccination in regional lymph nodes is the first reported in a Japanese patient. We should be aware of this new mimic and optimize diagnostic imaging methods accordingly in the era of COVID-19.
Sarcoidosis is a chronic inflammatory disease of unknown etiology that affects many systemic organs, including the eye. The eye is the second most frequently affected organ in patients with sarcoidosis after lung disease. Approximately 30-50% of patients with systemic sarcoidosis develop uveitis, which is a sight-threatening intraocular inflammatory disorder. Sarcoidosis is the leading cause of uveitis in Japan and is one of the major clinical entities in many countries. Therefore, uveitis in association with sarcoidosis (ocular sarcoidosis) is considered essential in clinical practice in ophthalmology. The current review focuses on distinguishing features of ocular sarcoidosis, diagnosis, management, and discussion of the etiology of ocular sarcoidosis.