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Tumoral calcinosis (TC) is a syndrome of unknown etiology characterized by calcium salt deposition in soft tissues. 1 A case of infected TC with rheumatoid arthritis (RA) is described.

Objective: To investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM)., Methods: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl t-RNA synthetase antibodies in the DM patients (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis (GSVA) to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach., Results: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and -negative monocytes and myeloid dendritic cells. Notably, DM patients demonstrated enrichment of complement and interferon-α and -γ pathway genes compared to those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and transforming growth factor-β signaling pathway., Conclusion: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathological differences among IIM subtypes. DM was characterized by complement, interferon-α and -γ signaling, whilst ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype., (This article is protected by copyright. All rights reserved.)

Objectives: Hydroxychloroquine (HCQ) is recommended at a target dose of 5 mg/kg per actual body weight to reduce the risk of retinopathy in systemic lupus erythematosus (SLE). However, the efficacy of HCQ has been established at doses of 6.5 mg/kg per ideal body weight. This study aimed to clarify the effects of the HCQ dose on the continuation rate in Japanese patients, who generally have a lower body mass index than Western patients., Methods: This retrospective single-centre observational study enrolled patients with SLE on HCQ therapy. Patients were divided into two groups with a dose per actual body weight [the low-dose (<5 mg/kg) group and the high-dose (≥5 mg/kg) group], and continuation rates were compared. The efficacy of 1-year HCQ therapy was assessed in patients without additional immunosuppressive agents and biologics., Results: Of the 231 patients enrolled, 48 (20.8%) discontinued HCQ. The HCQ dose per actual body weight was identified as an independent risk factor for discontinuation. The low-dose group showed a significantly higher 1-year HCQ continuation rate than the high-dose group (83.2% vs. 72.8%, respectively). Both groups showed reductions in glucocorticoid requirement and serological activity after 1-year HCQ therapy., Conclusions: HCQ <5 mg/kg per actual body weight may facilitate greater continuation., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relationship between clinical signs of PVOD and severity of pulmonary vasculopathy in SSc., Methods: This study included 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities [mean pulmonary arterial pressure (mPAP) >20 mmHg, pulmonary vascular resistance >2 WU or pulmonary artery wedge pressure (PAWP) >15 mmHg]. A chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function and serum biomarkers were compared between the two groups., Results: Mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity were observed in 11 (21%), 32 (62%) and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (P = 0.02) but lower diffusing capacity of carbon monoxide (DLCO)/alveolar volume (P = 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide and Krebs von den Lunge-6 were not different between the two groups., Conclusions: The CT signs for PVOD had a positive correlation with mPAP but a negative correlation with DLCO in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown., Methods: A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m 2 /week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months)., Results: A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025)., Conclusion: At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted., Trial Registration Number: NCT02198248., Competing Interests: Competing interests: SF reports receiving lecture fees from Chugai Pharma (Roche group), Asahi Kasei Pharma, Eisai, Daiichi Sankyo and Kissei Pharma and consulting fee from Asahi Kasei Pharma. DN reports receiving grant support and lecture fees from Asahi Kasei Pharma, Chugai Pharma (Roche group), Eisai and Taisho Pharma. MH reports receiving travel support or lecture fees from GlaxoSmithKline, Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, AbbVie, Eli Lilly, Bristol-Myers Squibb, Sanofi, Takeda Pharmaceutical, AstraZeneca, Taisho Pharmaceutical, Pfizer, UCB Japan, Gilead Science, Novartis Pharmaceuticals and Mitsubishi Tanabe Pharma. KA reports receiving lecture fees from AbbVie, Chugai Pharma (Roche group), Eisai, Eli Lilly, GlaxoSmithKleine, Mitsubishi Tanabe Pharma and Pfizer Japan. TU reports receiving lecture fees from Asahi Kasei Pharma, AbbVie GK, Eli Lilly, Mitsubishi Tanabe Pharma and Pfizer, Astellas Pharma, Takeda Pharma, Eisai, Bristol-Myers Squibb and Gilead Sciences. HK reports receiving lecture fees from Chugai Pharma (Roche group), Astellas Pharma, AbbVie, Takeda Pharma, Pfizer, Asahi Kasei Pharma, Eisai and Teijin Pharma. KK reports receiving grant support from AbbVie, Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Japan blood products organisation, Mitsubishi Tanabe Pharma, Ono Pharma and Taisyo Pharmaceutical and lecture fees from AbbVie, Asahi Kasei Pharma, Chugai Pharmaceutical, Eli Lilly Japan, Eisai and GSK. RM reports receiving lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly Japan and GSK. YKa reports receiving grant or lecture fees from AbbVie, Asahi Kasei Pharma, Astellas Pharma, Ayumi, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Jansen, Kirin, Novartis Pharma, Pfizer, Sanofi, Takeda Pharma, Mitsubishi Tanabe Pharma and UCB. KH reports receiving consulting fee from GSK, grant support from Chugai Pharma, GSK, Bayer Yakuhin and Kyowa Kirin, and lecture fees from Chugai Pharma, Astellas Pharma, AstraZeneca, Sanofi, GSK and Asahi Kasei Pharma. S-iK reports receiving lecture fees from Janssen Pharmaceutical, AbbVie and VIATRIS and consulting fee from Asahi Kasei Pharma. KI reports receiving grant support from Mitsubishi Tanabe Pharma and lecture fees from Mitsubishi Tanabe Pharma, Bristol-Myers Squibb, Novartis Pharma, AbbVie, Gilead Sciences, Eisai and Eli Lilly. HN reports receiving grant support or lecture fees from Chugai Pharma (Roche group), Bristol-Myers Squibb, Asahi Kasei Pharma, Mitsubishi Tanabe Pharma, Eli Lilly Japan, Eisai, AbbVie, GSK, Sanofi, Novartis Pharma, AstraZeneca and Astellas Pharma. Any pharmaceutical company was not involved in the planning of the protocol or in the conduct of the trial. No other potential conflict of interest relevant to this article was reported., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype., Methods: Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin-sequencing., Results: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRA high synovial fibroblasts, autoimmune-associated B cells, GZMK + GZMB + CD8 + T cells, interleukin (IL)1-β + monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)-α, interferons (IFNs), and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively., Conclusion: This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Nintedanib is an inhibitor of tyrosine kinases that has been shown to slow the progression of interstitial lung disease (ILD), including ILD associated with SSc. The aim of this study was to explore the effect of nintedanib on cardiomyopathy associated with systemic sclerosis (SSc)., Methods: Twenty consecutively hospitalized patients with SSc-ILD were enrolled and prospectively followed. The rate of change at 6 months in cardiac magnetic resonance (CMR) parametric mapping, including myocardial extracellular volume, was primarily evaluated. Other endpoints included changes in CMR functional parameters, echocardiographic parameters, modified Rodnan skin score, serum biomarkers and pulmonary function test., Results: Nintedanib was administered in 10 patients, whereas the other 10 were treated without nintedanib or watched, according to ILD severity and progression. Baseline values of CMR parametric mapping were not different between the two groups. The rate of change at 6 months in myocardial extracellular volume was highly different, almost divergent, between the nintedanib group and the control group (-1.62% vs +2.00%, P = 0.0001). Among other endpoints, the change in right ventricular ejection fraction was significantly different between the two groups (P = 0.02), with a preferential change in the nintedanib group., Conclusion: Our data indicate beneficial signals of nintedanib on cardiomyopathy associated with SSc. The anti-fibrotic effect of nintedanib might not be limited to the lung., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Systemic sclerosis (SSc) is associated with pulmonary vascular disease and interstitial lung disease, making it difficult to differentiate pulmonary arterial hypertension and pulmonary hypertension (PH) due to lung diseases and/or hypoxia and to decide treatments. We aimed to predict the response to pulmonary vasodilators in patients with SSc and PH., Methods: Eighty-four SSc patients were included with 47 having PH. Chest computed tomography was evaluated using software to calculate the abnormal lung volume (ALV). To define the response to vasodilators, Δ mean pulmonary artery pressure (mPAP)/basal mPAP was used (cut-off value: 10%). The predictive value was evaluated by using the receiver operating characteristic curve., Results: The mean (±standard deviation) value of ALV was 26.8 (±32.2) %. A weak correlation was observed between ALV and forced vital capacity (FVC) (R = -0.46). The predictive value of ALV [area under curve (AUC) = 0.74] was superior to that of FVC (AUC = 0.62) for the response to vasodilators. No hemodynamic parameters differed between patients with high and low ALV, whereas survival was worse in high ALV., Conclusions: Quantitative chest computed tomography well predicted the response to vasodilators in patients with SSc and PH. Our results suggest its utility in differentiating the dominance of pulmonary vascular disease or interstitial lung disease., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) is of clinical significance owing to its poor outcome. One of the explanations for the outcome is the co-presence of left heart disease (LHD). The aim of this study is to assess LHD phenotype in patients with SSc and pulmonary hypertension (PH)., Methods: This study included consecutive patients with SSc who underwent right heart catheterisation to diagnose PAH. Heart failure with preserved ejection fraction (HFpEF) was evaluated according to the recommendation of 6th WSPH and to the Framingham criteria., Results: In total, 76 patients were enrolled in this study. Of them, 42 had PH (mPAP >20 mmHg) with a normal left ventricle ejection fraction (≥50%). Among the 42 patients, four and three patients were classified "HFpEF not excluded" and "HFpEF confirmed" whereas 10 had a clinical diagnosis of HFpEF according to 6th WSPH and Framingham criteria, respectively. These differences were due mainly to relatively low PAWP (<13 mmHg). By a combination of ROC curve and logistic regression analyses, left atrial dimension and left ventricular end-diastolic volume index assessed with echocardiography and cardiac MRI, respectively, had significantly higher predictive values for detecting the complication of HFpEF rather than PAWP., Conclusions: Morphological evaluation using echocardiography and cardiac MRI, compared with haemodynamic evaluation by PAWP, may better reflect the copresence of LHD phenotype in patients with SSc and PH. Our data would also indicate a limited elevation of PAWP in patients with SSc, PH and HFpEF.

Importance: The current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis is the combination of high-dose glucocorticoids and cyclophosphamide or rituximab. Although these regimens have high remission rates, they are associated with considerable adverse events presumably due to high-dose glucocorticoids., Objective: To compare efficacy and adverse events between a reduced-dose glucocorticoid plus rituximab regimen and the standard high-dose glucocorticoid plus rituximab regimen in remission induction of ANCA-associated vasculitis., Design, Setting, and Participants: This was a phase 4, multicenter, open-label, randomized, noninferiority trial. A total of 140 patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage were enrolled between November 2014 and June 2019 at 21 hospitals in Japan. Follow-up ended in December 2019., Interventions: Patients were randomized to receive reduced-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n = 70) or high-dose prednisolone (1 mg/kg/d) plus rituximab (n = 70)., Main Outcomes and Measures: The primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was -20 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections., Results: Among 140 patients who were randomized (median age, 73 years; 81 women [57.8%]), 134 (95.7%) completed the trial. At 6 months, 49 of 69 patients (71.0%) in the reduced-dose group and 45 of 65 patients (69.2%) in the high-dose group achieved remission with the protocolized treatments. The treatment difference of 1.8 percentage points (1-sided 97.5% CI, -13.7 to ∞) between the groups met the noninferiority criterion (P = .003 for noninferiority). Twenty-one serious adverse events occurred in 13 patients in the reduced-dose group (18.8%), while 41 occurred in 24 patients in the high-dose group (36.9%) (difference, -18.1% [95% CI, -33.0% to -3.2%]; P = .02). Seven serious infections occurred in 5 patients in the reduced-dose group (7.2%), while 20 occurred in 13 patients in the high-dose group (20.0%) (difference, -12.8% [95% CI, -24.2% to -1.3%]; P = .04)., Conclusions and Relevance: Among patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage, a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission at 6 months., Trial Registration: ClinicalTrials.gov Identifier: NCT02198248.

Hypophosphatasia (HPP) is caused by mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene in an autosomal recessive or dominant manner and characterized by defective mineralization of bone and low serum ALP levels. In this report, we present a family with HPP mother (case 1) and HPP child (case 2) who have identical TNSALP gene mutation (c.1015G>A p.Gly339Arg heterozygous mutation) but distinct clinical phenotypes. Whereas case 1 appeared to be asymptomatic despite extremely low levels of serum ALP, case 2 had several HPP-related symptoms, such as tooth loss, fractures, short stature, with slightly decreased ALP levels. Upon the diagnosis of HPP, case 1 discontinued denosumab, which was used to treat her rheumatoid arthritis, concerning the risk of atypical femoral fractures. The clinical course of this family was suggestive in a genotype-phenotype imbalance in HPP, the underdiagnosis of HPP in adults, and the risk of atypical femoral fractures using bone resorption inhibitors.

Infectious disease with various presentations in systemic lupus erythematosus often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic synovitis with epithelioid granuloma. A mycobacterial culture confirmed invasive mycobacterial tenosynovitis due to Mycobacterium chelonae. The patient was treated with moxifloxacin and clarithromycin and completely recovered.

Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20 mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right heart catheterization (RHC) in our hospital during 2010-2018. Following variables were assessed for performance to predict mPAP ≥ 25 mmHg or > 20 mmHg; anti-centromere or U1-RNP antibody, plasma BNP level, serum urate level, right axis deviation, forced vital capacity (FVC)/diffusing capacity for carbon monoxide (DLCO) ratio, and tricuspid regurgitation velocity. Of 58 patients enrolled in this study, 24 had mPAP of ≥ 25 mmHg and 9 had mPAP of 21-24 mmHg. Among variables tested, only FVC/DLCO elevated similarly in patients with mPAP of ≥ 25 mmHg (median 2.5) and those with mPAP of 21-24 mmHg (median 2.5) compared to those with mPAP of ≤ 20 mmHg (median 1.5). Given the particularly good correlation between DLCO and mPAP of > 20 mmHg, each variable was weighted according to its odds ratio and the total weighted score was calculated. The total weighted score exhibited a good predictive performance for mPAP of > 20 mmHg with its sensitivity of 87.5% and specificity of 92%. Among conventional risk factors for PAH, decreased DLCO may predict mPAP > 20 mmHg with priority in SSc patients. Weighting DLCO may improve the performance of screening algorithm for early SSc-PAH.

We report a systematic spectroscopical investigation of three plagioclase particles (RB-QD04-0022, RA-QD02-0025-01, and RA-QD02-0025-02) returned by the Hayabusa spacecraft from the asteroid Itokawa, by means of scanning electron microscopy, cathodoluminescence microscopy/spectroscopy, and micro-Raman spectroscopy. The cathodoluminescence properties are used to evaluate the crystallization effects and the degree of space weathering processes, especially the shock-wave history of Itokawa. They provide new insights regarding spectral changes of asteroidal bodies due to space weathering processes. The cathodoluminescence spectra of the plagioclase particles from Itokawa show a defect-related broad band centered at around 450 nm, with a shoulder peak at 425 nm in the blue region, but there are no Mn- or Fe-related emission peaks. The absence of these crystal field-related activators indicates that the plagioclase was formed during thermal metamorphism at subsolidus temperature and extreme low oxygen fugacity. Luminescence characteristics of the selected samples do not show any signatures of the shock-induced microstructures or amorphization, indicating that these plagioclase samples suffered no (or low-shock pressure regime) shock metamorphism. Cathodoluminescence can play a key role as a powerful tool to determine mineralogy of fine-grained astromaterials.