Seminars in arthritis and rheumatism最新文献

Immune checkpoint molecules like PD-1 and its ligand PD-L1 and CTLA-4 are important regulators of the immune system. Medications blocking these pathways, immune checkpoint inhibitors, have been used to treat a variety of malignancies, while drugs agonizing these pathways, like abatacept, have been used in treating autoimmune diseases. Modulation of the PD-1/PD-L1 axis has become important for rheumatologists to understand in several different clinical scenarios. Currently, PD-1 agonists are being developed for treatment of rheumatoid arthritis (RA). In addition to patients with RA being potentially treated with PD-1 agonists, patients with rheumatoid arthritis may be treated with anti-PD-1/PD-L1 immune checkpoint inhibitors if they develop cancer. Finally, patients treated with immune checkpoint inhibitors may develop de novo inflammatory arthritis and be referred to rheumatology for management. In all three scenarios, there remain many unanswered clinical and translational questions. The parallel development of therapeutics antagonizing and agonizing the PD-1/PD-L1 pathway presents a unique chance for discovery in inflammatory arthritis.

Objectives: To gather the perspectives of APS ACTION members regarding the strengths and limitations of Damage Index for Antiphospholipid Syndrome (DIAPS); and establish recommendations for the improvement of DIAPS.

Methods: APS ACTION members were invited to answer a survey regarding their satisfaction with DIAPS scoring system and individual items. The level of agreement (LoA) among members with the inclusion of individual items in DIAPS was calculated (LoA of <75% was considered disagreement). Respondents' open-ended comments about DIAPS limitations were also collected, which helped formulate our recommendations for DIAPS improvement.

Results: Forty-two APS ACTION members (58.3%) answered the survey. Of them, 26 (61.9%) were satisfied, 4 (9.5%) were neutral, and 12 (28.6%) were dissatisfied with the current DIAPS scoring system. Fifteen items (39.5%) presented a LoA <75% regarding the inclusion in DIAPS. Respondents provided comments that were grouped under six main categories related to concerns about: a) definitions and attribution of damage (including causality and temporal relationship); b) scoring system; c) overlapping items; d) specific items (exclusion of redundant items and inclusion of additional ones); e) the need to incorporate multiple events; and f) feasibility and practicality. Finally, the APS ACTION "Damage" Working Group developed 7 recommendations that should be considered for the next generation DIAPS.

Conclusion: Approximately 60% of respondents were satisfied with DIAPS and its definitions; however, our survey demonstrated that there is substantial room to improve the current damage index for APS. Efforts for updating DIAPS should consider the APS ACTION "Damage" Working Group recommendations.

Objective: Few studies have examined peripartum maternal outcomes in systemic lupus erythematosus (SLE). Using a de-identified electronic health record (EHR) cohort of individuals with and without SLE, we compared rates of peripartum maternal outcomes including maternal infections, blood transfusions, hospital length of stay, and SLE flares.

Methods: We identified deliveries among individuals with SLE and individuals without autoimmune disease using a previously validated algorithm. Peripartum maternal infection was assessed up to 6 weeks postpartum. Using Chi-square and Mann-Whitney U tests, we compared peripartum outcomes in SLE and control deliveries. We performed mixed effects models to estimate the association of SLE case status with peripartum outcomes. We assessed for SLE flares up to 6 months postpartum using chart review of rheumatology notes and the 2009 revised SELENA Flare Index. We evaluated SLE medications prescribed during pregnancy and at time of delivery on peripartum outcomes.

Results: We identified 185 deliveries to 142 individuals with SLE and 468 deliveries to 241 control individuals without autoimmune diseases. Mean length of hospital stay was longer for individuals with SLE compared to controls (3.1 ± 2.0 vs. 2.4 ± 1.0 days, p < 0.001). In a mixed effects model, peripartum infection was significantly associated with SLE case status (OR = 6.18, 95 % CI 2.73 - 13.98, p < 0.01), Cesarean section (OR = 5.00, 95 % CI 2.16 - 11.57, p < 0.01), and age at delivery (OR = 0.92, 95 % CI 0.86 - 0.99, p = 0.03) after adjusting for race. Transfusion was also significantly associated with SLE case status (OR = 9.05, 95 % CI 3.24-25.32, p < 0.01) and Black race (OR = 6.64, 95 % CI 1.47 - 30.02, p = 0.01) after adjusting for Cesarean section and age at delivery. We observed a postpartum flare rate of 32 % among individuals with SLE with 13 % characterized as mild, 41 % moderate, and 46 % severe. Antimalarial use in the postpartum period was associated with lower flare rate (43 % vs. 63 %, p = 0.04).

Conclusions: Individuals with SLE have increased rates of blood transfusions, longer hospital stays, and more frequent infections compared to control individuals in the peripartum period. We observed a postpartum flare rate of 32 %, and antimalarial use was associated with lower flare rate. Our findings demonstrate that the peripartum period remains a high-risk time for individuals with SLE with an ongoing need for close monitoring.

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Objectives: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) face excess mortality compared with the general population. Mortality in clinical epidemiology research is often examined using death certificate diagnosis codes; however, the sensitivity of such codes in AAV is unknown.

Methods: We performed a retrospective cohort study using the Mass General Brigham AAV Cohort, including patients with AAV who died between 2002 and 2019. Causes of death were determined by electronic health record (EHR) review (reference gold standard) and via cause of death diagnosis codes on death certificates. We calculated the sensitivity of death certificate diagnosis codes for AAV.

Results: Of 684 patients in the registry, 184 died, 92 (52 %) of whom had adequate EHR data available determine cause of death and 72 (40 %) of whom had both EHR and death certificate data available. Death due to AAV, infection, cardiovascular disease, and cancer occurred in 8 %, 29 %, 5 %, and 18 %, respectively, when ascertained by manual review, as opposed to 0 %, 11 %, 25 %, and 21 %, as determined by death certificates. The sensitivity of AAV diagnosis codes for AAV was 16.6 % (95 % CI: 10.5, 22.6) among all patients with death certificate data available.

Conclusion: In a contemporary cohort of patients with AAV, infection was the most common cause of death, while death due to AAV itself was rare. We found a high degree of discordance between causes of death determined by manual review and death certificate diagnosis codes. Mortality research on AAV should include linkage to medical records data to reduce potential bias.

Introduction: Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a promising treatment for hematological malignancies. However, its association with immune-related complications such as rheumatic complications, is not well defined.

Methods: We conducted a retrospective study to analyze rheumatic complications in 310 patients treated with CAR-T therapy at a single center from January 2020 to May 2024.

Results: We identified six patients (1.9 %) who developed rheumatic complications, including rheumatoid arthritis (RA)-like manifestations with biopsy-proven nodules, palindromic rheumatism, myositis, necrotizing fasciitis, and osteonecrosis (ON). Symptoms appeared between 2 to 11 weeks after therapy, with inflammatory arthritis manifesting later. Notably, 2 patients developed RA-like arthritis with subcutaneous nodulosis, while others presented with transient arthritis flares, severe soft tissue and joint involvement, such as pseudo-podagra and ON. Imaging findings and biopsies confirmed the diagnoses. Treatment included glucocorticoids, hydroxychloroquine, and nonsteroidal anti-inflammatory drugs, with variable responses.

Conclusions: Clinicians should be aware of these potential complications to ensure prompt diagnosis and management. Further research is needed to elucidate the mechanisms underlying these autoimmune phenomena and to establish standardized treatment protocols.

Objective: The study aimed to investigate the damage of white matter (WM) microstructure and structural network in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging.

Methods: Tract-based spatial statistics (TBSS) were used to compare the difference in WM fractional anisotropy (FA) between SLE and HCs groups. The differences in WM networks between groups are compared using graph theory. The correlation between clinical data and SLE abnormal WM structure and network was analysed.

Results: The sample included 140 SLE patients and 111 healthy controls (HCs). Due to data missing, excessive head movement amplitude, failure of quality control and other reasons, 127 cases of SLE (103 females, mean age 29.84 years (SD 7.00), median years of education 12.00, interquartile range(9.00,15.00) and a median course of disease (month) 12.00, interquartile range (3.00,24.00)) and 102 cases of HCs (76 females, mean age 30.63 years (SD 7.24), median years of education 15.00, interquartile range(12.00,16.00)) were finally included in the study. The FA values of 5 clusters involving the right retrolenticular part of the internal capsule (RLIC), the genu of corpus callosum (GCC), the body of corpus callosum, the splenium of corpus callosum (SCC), were significantly lower in the SLE group compared to the HCs (P < 0.05 with threshold-free cluster enhancement corrected). The SLEDAI showed a negative correlation with FA in GCC, and HAMD showed a negative correlation with FA in SCC and right RLIC (P < 0.05). Regarding network indicators, Cp, E_glob, and E_loc were significantly decreased, while Lp was significantly increased in the SLE group. The degree centrality (DC) of 6 brain regions and the E_nodal of 17 regions were significantly lower in the SLE group. SLEDAI showed a negative correlation with the area under the curve (AUC) of DC and E_nodal in the left inferior frontal gyrus triangular (q < 0.05 with false discovery rate corrected), while MMSE showed a positive correlation with the E_nodal in the left hippocampus (P < 0.05).

Conclusion: The study concludes that changes in WM microstructure and its structural network may contribute to the development of severe neuropsychiatric symptoms in SLE patients. These changes may be the basis of brain damage that leads to the development of NPSLE from SLE without major neuropsychiatric manifestations.