Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

Vanishing Abdominal Aorta.

Fewer than 1% of Takayasu arteritis (TA) cases are diagnosed in individuals over 60 years old.1 Early-stage TA generally presents with nonspecific systemic inflammatory symptoms, which can progress to the chronic, fibrotic occlusive phase,2 although there is significant heterogeneity in disease activity.3.

Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome.

OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median onset age (IQR) 69.3 years (62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants, and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR (pdPCR) or targeted amplicon deep sequencing (TAS) was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and ­negative patients and assessed the diagnostic value of our system using receiver operating characteristic (ROC) curve analysis. RESULTS: Forty patients with reported pathogenic UBA1 variants (40/89, 44.9%) were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering >50 years of age, cutaneous lesions, lung involvement, chondritis, and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSIONS: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.

Safety of tacrolimus use during pregnancy and related pregnancy outcomes in patients with systemic lupus erythematosus: A retrospective single-center analysis in Japan.

OBJECTIVE: Tacrolimus is one of the drugs that can be used in pregnancies complicated with systemic lupus erythematosus (SLE), but there are still few reports on its pregnancy outcomes. Although tacrolimus has been reported to cause adverse events, such as increased blood pressure, abnormal glucose metabolism, and susceptibility to infection, there have been no studies on the impact of tacrolimus in SLE pregnancies at these points. We performed a retrospective observational study of pregnancies complicated by SLE at St Luke's International Hospital in Tokyo from April 2003 to August 2021. METHODS: Basic clinical information on SLE, pregnancy outcomes, disease activity before and after pregnancy, laboratory results, blood pressure, blood glucose levels, treatment regimens, and presence of infection was extracted from electronic medical records. We defined overall adverse pregnancy outcomes (APOs) as follows: (1) fetal death after 10 gestational weeks, (2) preterm delivery, (3) delivery due to hypertensive disorders of pregnancy, preeclampsia, or placental insufficiency, or (4) the diagnosis of small for gestational age infants. We also examined whether there was a statistical difference in APO incidence between patients treated with and without tacrolimus. RESULTS: Pregnancy outcomes were obtained for 48 patients with a total of 60 pregnancies complicated by SLE. In 20 (33.3%) of these pregnancies, the patients took tacrolimus, and 28 (46.7%) of the pregnancies had APOs. APO incidence did not statistically differ between the tacrolimus and non-tacrolimus groups in the multivariate analysis (p = 1.00, adjusted OR 1, 95% CI: 0.23-4.39). Multiple regression analyses indicated that tacrolimus use did not significantly affect systolic blood pressure in the third trimester (B = -2.23, p = .74) or blood glucose levels in the first trimester (B = 10.2, p = .056). Incidence of infections did not significantly differ between patients treated with and without tacrolimus in the univariate analysis (10.8% vs. 21.1%, p = .42). CONCLUSION: Tacrolimus did not significantly affect pregnancy outcomes, blood pressure, or glucose levels. Further research is required to confirm its effects in a larger population.

Shared decision-making practices and patient values in pharmacist outpatient care for rheumatic disease: A multiple correspondence analysis.

Purpose: To investigate the value-to-value relationships, relationship between values and patient background, continuation rate of treatment after shared decision-making (SDM), and disease status in order to clarify the values involved in drug therapy decisions for patients with rheumatic disease. Methods: We investigated patient values (efficacy of drug therapy [effectiveness], safety, economics, daily life, and other) and the continuance rate and disease status of treatment after 6 months in 94 patients with rheumatic disease aged ≥18 years who made decisions with pharmacists and physicians in the pharmacy outpatient clinic between September 2019 and April 2021. Multiple correspondence and K-means cluster analyses were performed to show the relationship between values and basic patient information. Results: Among the selected patients, 87% and 47% selected effectiveness for multiple selections and single selection, respectively. Effectiveness was at the center of the graph; three clusters containing other values were placed around it. History of allergy or side effects caused by biologics or Janus kinase inhibitors were in the safety cluster. The non-usage history of biologics or Janus kinase inhibitors was in the economic cluster. Conclusion: Effectiveness was the most important factor for patients with rheumatic disease; the values that patients consider important may shift from effectiveness to other values based on each patient's subjective experience with the treatment and/or the stage of life in which they were treated. It is important to positively link patient values and information about the treatment plan in shared decision-making while establishing rapport with the patient.

Concomitant use of intravenous methylprednisolone to increase retention rate of abatacept in rheumatoid arthritis.

To investigate whether concomitant use of intravenous methylprednisolone (IVMP) with Abatacept (ABA) contributes to earlier remission and higher drug retention rates. This was a retrospective cohort study to assess the retention rate of ABA in rheumatoid arthritis (RA) patients treated at a single center in Japan from January 2010 to May 2017. Patients were divided into an ABA monotherapy group and ABA IVMP group. IVMP (40 mg) was administered with the first three consecutive doses of ABA. ABA retention rates were evaluated using Kaplan-Meier analysis. Hazard ratios for the drug retention rate were also calculated as the sensitivity analysis. A total of 59 seropositive RA patients were analyzed. Twelve patients were treated with ABA IVMP, and 47 patients were treated with ABA monotherapy. The overall ABA retention rate was 76.3% at 24 weeks. The retention rates were 91.7 and 72.3% in the ABA IVMP and ABA monotherapy groups, respectively. Log-rank analysis revealed no statistical difference between the two groups (p = 0.17). The sensitivity analysis showed that the hazard ratio of IVMP was 2.9-3.7 in three models, although there was no statistical significance. Safety analysis revealed that no patients discontinued ABA because of adverse events in the ABA IVMP group, while 7/47 (14.9%) discontinued the drug in the ABA monotherapy group. In this real life study, ABA, concomitantly used with IVMP, showed numerically higher retention rates without additional safety signals, although there was no statistical significance. Concomitant use of IVMP may help RA patients achieve earlier remission.

Safety and efficacy of upfront graded administration of trimethoprim-sulfamethoxazole in systemic lupus erythematosus: A retrospective cohort study.

OBJECTIVES: Trimethoprim-sulfamethoxazole (TMP/SMX) is effective as prophylaxis against many infections in immunocompromised patients. However, it is not commonly prescribed for patients with systemic lupus erythematous (SLE) due to the risk of adverse reactions (ADRs). An upfront graded administration protocol for TMP/SMX was adopted, and its safety and efficacy were assessed. METHODS: Data from 59 patients with SLE patients who received prophylactic TMP/SMX were retrospectively analyzed. The incidence and risk factors for ADRs in patients who received TMP/SMX before and after the introduction of graded administration were assessed. RESULTS: The incidence of ADRs was 41.9% in the non-graded administration group, vs. 10.7% in the graded administration group (p = 0.009). The rate of high fever, liver function test (LFT) abnormality, shortness of breath, and hospitalization were reduced in upfront graded administration group. In addition, a higher rate of anti-Ro/SS-A positivity was found in patients experienced ADRs (46.2% in reactors vs. 5.6% in non-reactors; p = 0.012) in the non-graded administration group. CONCLUSIONS: Upfront graded administration of TMP/SMX reduces the incidence and severity of ADRs in SLE patients. The high incidence of TMP/SMX ADRs in SLE patients was also confirmed, especially when anti-Ro/SS-A antibody is present.

Safety and efficacy of mizoribine in patients with connective tissue diseases other than rheumatoid arthritis.

The objective of this study was to examine the safety and efficacy of mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, in patients with connective tissue diseases (CTDs) other than rheumatoid arthritis. We identified all patients who had ever been treated with MZR for CTDs at our institution during the period from January 2001 to May 2011. A retrospective review of medical records was performed to evaluate safety and efficacy of MZR. A total of 63 patients (13 induction and 50 maintenance therapy with MZR) were included. During 70.2 patient-years of follow-up, only one patient required discontinuation of MZR due to an adverse event. Doses of PSL were significantly decreased at last follow-up in both the induction (45.2 ± 15.6 vs. 8.4 ± 5.7 mg/day, p < 0.01) and the maintenance group (12.4 ± 7.6 vs. 9.3 ± 6.4 mg/day, p < 0.01). MZR appears to be a safe and well-tolerated steroid-sparing agent in patients with CTDs.

Anti-asparaginyl tRNA synthetase (Anti-KS) antibody-positive pneumonitis in a patient with immune checkpoint inhibitor treatment: A case report and literature review.

In recent years, the use of immune checkpoint inhibitors (ICI) has increased and there have been case reports of anti- aminoacyl tRNA synthetase (ARS) antibody syndrome during ICI treatment. However, these cases are limited, and their clinical characteristics are not fully understood. We report the first case of anti ARS antibody syndrome with KS antibody during ICI therapy. This report presents our case, along with a literature review of other anti ARS antibody syndrome cases that developed after ICI use, discussing their clinical characteristics and possible mechanisms of onset. Considering the widespread use of ICI in cancer therapy, we should aware of anti ARS antibody syndrome that develops during use of ICI .

Self-remitting Bartonella neuroretinitis without a cat scratch.

•Bartonella infection is a leading cause in patients with neuroretinitis.•Ocular involvement occurs in 5-10% of people with cat-scratch disease (CSD).•Bartonella neuroretinitis presents without systemic signs and symptoms of CSD.•Some cases with bartonella neuroretinitis could be self-remitted.

Kidney biopsy in patients with antineutrophil cytoplasmic antibody-associated vasculitis with mild renal abnormality.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic inflammation of small or medium blood vessels that includes microscopic polyangiitis. A diagnosis of ANCA-associated vasculitis can be aided by histological identification of vasculitis, and identification of renal impairment can help predict outcomes. However, kidney biopsy is not generally indicated in the absence of renal findings. We report two cases of ANCA-associated vasculitis diagnosed by kidney biopsy despite the absence of remarkable urinary abnormality and renal impairment. These patients had fever of unknown origin and were positive for myeloperoxidase (MPO)-ANCA but showed few findings that would suggest small-vessel vasculitis in the kidney. Nevertheless, kidney biopsies revealed small-vessel arteritis, necrotizing glomerulonephritis, and interstitial nephritis. Immunofluorescent antibody tests performed using samples of glomeruli were all negative, suggesting microscopic polyangiitis. Therefore, kidney biopsy may be useful in confirming the diagnosis, even if patients have completely normal urinary findings in the absence of other organ lesions.

Current evidence and practical knowledge for ultrasound-guided procedures in rheumatology: Joint aspiration, injection, and other applications.

Ultrasound (US)-guided procedures have increasingly gained their role in the daily practice of rheumatology, owing to the growing evidence supporting their utility. The utilization of US guidance in procedures may enhance their accuracy, efficacy, and safety. This article presents a comprehensive review of the current evidence and practical knowledge pertaining to US-guided procedures in rheumatology, encompassing joint aspirations, injections, and other applications such as tendon sheath injections. We provide a detailed description of the US-guided procedure process and compare the in-plane and out-of-plane view methods, along with practical techniques based on existing evidence or our own expertise. For each joint, we summarize how to perform procedures with figures to facilitate a better understanding. Additionally, we introduce other applications of US-guided procedures for tendons, enthesis, bursae, and nerves as well as emerging therapies such as US-guided fascia hydrorelease. By utilizing these US techniques, rheumatologists can achieve the ability to manage a wider range of musculoskeletal conditions.

Effect of Prophylactic Dose of Trimethoprim-Sulfamethoxazole on Serum Creatinine in Japanese Patients With Connective Tissue Diseases.

Objectives: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. Methods: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. Results: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (-0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. Conclusions: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL.

Clinical Characteristics of Patients with Spondyloarthritis in Japan in Comparison with Other Regions of the World.

OBJECTIVE: To delineate clinical characteristics of patients with spondyloarthritis (SpA) in Japan in comparison to other areas of the world. METHODS: Using the ASAS-COMOSPA (Assessment of Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) data, an international cross-sectional observational study of patients with SpA, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Japan, other Asian countries (China, Singapore, South Korea, Taiwan), and non-Asian countries (Europe, the Americas, Africa). Patient characteristics, including diagnosis and treatment, were compared. RESULTS: Among 3984 patients included in the study, 161 were from centers in Japan, 933 from other Asian countries, and 2890 from other regions. Of patients with SpA in Japan, 42 (26.1%) had peripheral SpA, substantially more than in other countries. This trend was explained by the predominance of psoriatic arthritis (PsA) among Japanese patients with SpA. In contrast to the relatively low number in Japan, 54% of patients from other Asian countries had pure axial SpA (axSpA) without peripheral features. HLA-B27 testing, considered an integral part of the classification of axSpA, was performed in only 63.6% of Japanese patients with axSpA. More than half of Japanese patients with axSpA were classified using imaging criteria. CONCLUSION: In our study, there was a more substantial number of peripheral SpA cases observed in Japan compared to other parts of Asia and other regions of the world. Aside from ethnic differences, increasing recognition of PsA in Japan, as well as a potential underdiagnosis of axSpA due to the insufficient use of HLA-B27 testing, may partly explain regional discrepancies.