Analysis of Cytokine Profiles in Pediatric Myocarditis Multicenter Study.

Acute myocarditis (AM) is an inflammatory disease of the heart muscle that can progress to fulminant myocarditis (FM), a severe and life-threatening condition. The cytokine profile of myocarditis in children, especially in relation to fulminant myocarditis, is not well understood. This study aims to evaluate the cytokine profiles of acute and fulminant myocarditis in children. Pediatric patients diagnosed with myocarditis were included in the study. Cytokine levels were measured using a multiplexed fluorescent bead-based immunoassay. Statistical analysis was performed to compare patient characteristics and cytokine levels between FM, AM, and healthy control (HC) groups. Principal component analysis (PCA) was applied to cytokine groups that were independent among the FM, AM, and HC groups. The study included 22 patients with FM and 14 with AM patients. We identified four cytokines that were significantly higher in the FM group compared to the AM group: IL1-RA (p = 0.002), IL-8 (p = 0.005), IL-10 (p = 0.011), and IL-15 (p = 0.005). IL-4 was significantly higher in the AM group compared to FM and HC groups (p = 0.006 and 0.0015). PDGF-AA, and VEGF-A were significantly lower in the FM group than in the AM group (p = 0.013 and <0.001). Similar results were obtained in PCA. Cytokine profiles might be used to differentiate pediatric FM from AM, stratify severity, and predict prognosis. The targeted therapy that works individual cytokines might provide a potential treatment for reducing the onset of the FM and calming the condition, and further studies are needed.

GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.

Anti-survival motor neuron complex antibodies as a novel biomarker for pulmonary arterial hypertension and interstitial lung disease in mixed connective tissue disease.

OBJECTIVE: The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs. METHODS: A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of 35S-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed. RESULTS: Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs-positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs. CONCLUSIONS: Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD.

Association between aspirin dose and outcomes in patients with acute Kawasaki disease: a nationwide retrospective cohort study in Japan.

This study aimed to identify the appropriate dose of aspirin to be prescribed to patients with acute Kawasaki disease (KD). Using a Japanese national inpatient database, we identified patients with KD treated with intravenous immunoglobulin between 2010 and 2021.The outcomes included the occurrence of coronary artery abnormalities and intravenous immunoglobulin resistance, length of hospital stay, and medical costs. Restricted cubic spline functions were performed to examine the association between aspirin dose and the outcomes. Data of 82,109 patients were extracted from the database. Non-linear associations were observed between aspirin dose and the outcomes. In comparison with an aspirin dose of 30 mg/kg/day, the odds ratio (95% confidence interval) for coronary artery abnormalities was 1.40 (1.13-1.75) at 5 mg/kg/day. An aspirin dose of ≥ 30 mg/kg/day did not significantly change the odds ratio for coronary artery abnormalities. Intravenous immunoglobulin resistance was significantly lower at a dose of 60 mg/kg/day or higher. CONCLUSION:  The results showed no significant association between aspirin escalation over standard-dose and coronary artery abnormalities in patients with acute KD. High-dose aspirin showed the potential to reduce hospital stay and medical costs without increasing complications. WHAT IS KNOWN: • Aspirin is used as a standard treatment together with intravenous immunoglobulin for acute Kawasaki disease (KD). However, few studies have shown the most effective dosage of aspirin to prevent coronary artery abnormalities (CAAs). WHAT IS NEW: • There was no significant association between aspirin dose escalation and CAAs in patients with acute KD.

The electrophysiological index can effectively predict subsequent coronary artery aneurysm in children with Kawasaki disease.

Objectives: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. Methods: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). Results: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. Conclusions: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.

Serological analysis of severe acute respiratory syndrome coronavirus 2 infection in children with Kawasaki disease.

Multisystem inflammatory syndrome in children (MIS-C) was reported as a severe complication of coronavirus disease 2019; an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was suggested to be associated with Kawasaki disease (KD) in terms of severe systemic inflammation and mucocutaneous symptoms. Because severe gastrointestinal symptoms and systemic shock are more frequently observed with MIS-C, patients with mild MIS-C might have been diagnosed with KD. In this study, titers of IgG antibodies against the SARS-CoV-2 S (S-IgG) and N proteins (N-IgG) were measured in 99 serum samples collected from patients with KD treated between January 2020 and December 2021 to evaluate the relationship between KD and SARS-CoV-2 infection. S-IgG were detected in only one patient out of 99 patients. This patient had coronavirus disease 2019 (COVID-19) 10 months before KD onset, and was unlikely MIS-C. According to characters of S-IgG and N-IgG, the patients was unlikely infected with SARS-CoV-2 just before the onset of KD. In addition to this study, the 26th Nationwide Survey and previous studies showed an association between KD and SARS-CoV-2 to be unlikely. In conclusion, SARS-CoV-2 infection was not observed in patients with KD until Delta predominance in Japan by the method of detecting SARS-CoV-2 IgG.

Transport and Golgi organization 2 deficiency with a prominent elevation of C14:1 during a metabolic crisis: A case report.

Mutations in transport and Golgi organization 2 homolog (TANGO2) have recently been described as a cause of an autosomal recessive syndrome characterized by episodes of metabolic crisis associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration. Herein, we report a case of a one-and-a-half-year-old Japanese girl, born to nonconsanguineous parents, who presented with metabolic crisis characterized by hypoglycemia with hypoketonemia, rhabdomyolysis, lactic acidosis, and prolonged corrected QT interval (QTc) at the age of 6 months. Acylcarnitine analysis during the episode of crisis showed prominent elevation of C14:1, suggesting very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. In addition, worsening rhabdomyolysis was observed after intravenous administration of L-carnitine. VLCAD deficiency was initially suspected; however, the enzyme activity in lymphocytes was only mildly decreased at the gene carrier level, and no mutation in the VLCAD gene (ADADVL) was detected. Subsequently, acylcarnitine analysis was nonspecific at 17-h fasting and almost normal during the stable phase. Eventually, a trio whole-exome sequencing revealed a compound heterozygous variant of two novel variants in the TANGO2 gene, a missense variant, and a deletion of exon 7. This is the first case of TANGO2 deficiency in Asians. Our case suggests that elevated C14:1 may be seen in severe metabolic crises and that the use of L-carnitine should be avoided during metabolic crises.

Recommendations for the management of the vascular involvement in Behçet's disease by the Japanese National Research Committee for Behçet's disease-secondary publication.

OBJECTIVES: This study aimed to develop clinical guidelines for the management of vascular Behçet's disease (BD) by the Behçet's Disease Research Committee of the Ministry of Health, Labour and Welfare of the Japanese Government. METHODS: A task force proposed clinical questions (CQs) concerning vascular BD based on a literature search. After screening, draft recommendations were developed for each CQ and brushed up in three blinded Delphi rounds, leading to the final recommendations. RESULTS: This study provides recommendations for 17 CQs concerning diagnosis and differential diagnoses, assessment of disease activity, and treatment. The guidelines recommend immunosuppressive treatments, for both arterial and venous involvement with active inflammation. Anticoagulation is also recommended for deep vein thrombosis except in high-risk patients. Surgical and endovascular therapies can be optional, particularly in patients with urgent arterial lesions undergoing immunosuppression. In addition, two sets of algorithms for diagnosis and treatment are shown for arterial and venous involvement. CONCLUSIONS: These recommendations are expected to serve as useful tools in the daily clinical practice of BD. This content has already been published in Japanese in the Guideline for the Management of Behçet's Disease 2020 and is submitted with permission from both the primary and secondary publishers.

Association of steroid administration with larger coronary artery abnormalities in patients with Kawasaki disease.

We sought to elucidate the risk profiles of patients with Kawasaki disease who developed coronary artery abnormalities through a retrospective analysis with special reference to steroid treatment. Demographics of the patients were obtained from medical records, and characteristics of the coronary artery abnormalities were evaluated by echocardiography and coronary angiography, which included number, location, size, and length of coronary artery abnormalities (we evaluated by cardiac catheterisation with the American Heart Association classification with segments). We divided the patients into two groups based on steroid use and compared their characteristics and the complications of coronary artery abnormalities and cardiac events. A total of 29 patients were diagnosed with coronary artery abnormalities by echocardiography and coronary angiography during the study period (24 male; median age, 24 months [range: 2-84 months]). Eighteen patients were treated with aspirin and intravenous immunoglobulin (63%, non-steroid group), whereas 11 received aspirin and intravenous immunoglobulin plus steroids (37%, steroid group). No significant differences were found in the number and location of coronary artery abnormalities between the steroid and non-steroid groups. However, the size and number of segments for coronary artery abnormalities were significantly larger and shorter, respectively, in the steroid group (z-score: non-steroid group 6.3 versus steroid group 8.7; p < 0.01). The coronary artery abnormality segments under steroid use were also shorter (non-steroid group versus steroid group, two segments versus one segment; p = 0.02). Coronary artery abnormality size was larger in patients who used steroids than that of non-steroids. This study showed that steroid use significantly affected coronary artery abnormality size in patients with Kawasaki disease. However, cardiac complications from coronary artery abnormalities and cardiac events were comparable between the steroid and non-steroid groups. Further prospective, multicentre studies are needed to confirm these findings.

Usefulness of ultrasound as a predictor of elderly-onset rheumatoid arthritis with polymyalgia rheumatica-like onset.

OBJECTIVES: Differentiation between polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA), especially in elderly patients, is often difficult due to similarities in symptoms and serological kinetics. In this study, we aimed to analyse the predictors of EORA with PMR-like onset. METHODS: Seventy-two patients diagnosed with PMR, who attended our hospital for routine care and underwent musculoskeletal ultrasonography at that time were evaluated. Synovitis was evaluated semi-quantitatively (0-3) by grey scale (GS) and power Doppler (PD) in 24 joints [both hands (wrist, metacarpophalageal, and proximal interphalangeal joints) and both shoulder joints]. RESULTS: Overall, 18 patients had rheumatoid arthritis (25.0%); the mean age was 75.0 years, and 34.7% and 65.3% were male and female, respectively. In PMR and PMR/EORA groups, multivariate logistic analysis showed that rheumatoid factor positivity, GS ≥2 of hand joints, and PD ≥1 of hand joints were independent factors with significant differences. At least one of the three factors had a sensitivity of 88.9% and specificity of 92.6%. CONCLUSIONS: The presence of at least one of the criteria: rheumatoid factor positivity, GS ≥ 2, and PD ≥ 1 of hand joints, suggested the possibility of developing EORA within 1 year of PMR diagnosis.

A case of giant cell arteritis complicated by polymyalgia rheumatica with scalp necrosis and refractory jaw claudication.

Scalp necrosis is a rare complication of giant cell arteritis (GCA); however, it is a predictor of severe disease. In this case study, a patient presented with GCA complicated by polymyalgia rheumatica with scalp necrosis. An 86-year-old woman was admitted to the hospital for pulsating headache, scalp pain, jaw claudication, and generalised pain. Bilateral temporal arteries were found to be distended and pulseless, and scalp necrosis was observed in the parietal region. Simultaneous high-resolution contrast-enhanced magnetic resonance imaging (MRI) sequences of the head, shoulder, and hip showed staining around the bilateral shallow temporal arteries, shoulder, and hip joints, which was confirmed as GCA with polymyalgia rheumatica using other examination findings. After treatment with early induction remission therapy, scalp necrosis healed, but jaw claudication persisted. Six months after the start of treatment, scalp necrosis was cured to full hair growth. Despite remission induction therapy combined with tocilizumab, the patient had persistent jaw claudication for several months. At that time, a high-resolution contrast-enhanced MRI re-examination was useful in assessing disease activity. GCA with scalp necrosis may cause prolonged jaw claudication reflecting the progression of ischaemic lesions, whereas the disease activity can be accurately assessed by combining MRI studies.

A double heterozygous variant in MYH6 and MYH7 associated with hypertrophic cardiomyopathy in a Japanese Family.

Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous. Different variants associated with HCM have been identified in several cardiac sarcomeric protein genes. We identified the heterozygous missense variant c.2191 C>A p. Pro 731 Thr in the MYH7 gene and the heterozygous frameshift variant c.1091-1092 insTGAA p.Lys364fs*in the MYH6 gene in a Japanese family. Family members with the double variants demonstrated severe phenotypes, such as sudden cardiac-related death and heart failure. These double variants were well segregated and might be responsible for the severity of cardiovascular events in affected family members. These double variants are potentially associated with specific phenotypes in HCM. Further studies are needed to analyze specific gene functions. .

Atresia of the right coronary arterial ostium with a left ventricular fistula: A case report.

We describe the case of a young patient with atresia of the right coronary arterial ostium with left ventricular fistula. This was suspected from the abnormality detected on a 12­lead electrocardiogram (ECG) during a school examination at the time of admission to junior high school and echocardiography findings. This disease may occur due to abnormalities in several molecules that are essential for coronary artery development. In cases of ECG abnormality, and unexplained aortic valve regurgitation and coronary artery abnormalities on echocardiography are detected, this disease should be suspected. Learning objective: Coronary artery anomalies have been identified in coronary angiograms. Herein, we describe the case of a young patient with atresia of the right coronary arterial ostium with left ventricular fistula. This disease may be caused by abnormalities in several molecules that are essential molecule for coronary artery development.

Association between intravenous immunoglobulin dose and outcomes in patients with acute Kawasaki disease.

The most effective dosage of intravenous immunoglobulin (IVIG) to prevent coronary artery abnormalities (CAAs) in patients with acute Kawasaki disease (KD) remains unknown. This study aimed to identify the appropriate dose of IVIG to be administered to patients with acute KD, using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2020. The primary outcome was the proportion of CAAs upon discharge. Secondary outcomes included IVIG resistance, length of stay, and medical costs. Data from 88,223 patients were extracted from the database. We found a U-shaped association between IVIG dose and the proportion of CAA, with the bottom of the curve at approximately 2.0 g/kg; the odds ratio (95% confidence interval [CI]) was 1.34 (1.26-1.43) for 1.8 g/kg and 1.80 (1.29-2.51) for 2.4 g/kg with reference to 2.0 g/kg for CAA. Similarly, IVIG dose had a U-shaped association with the proportion of IVIG resistance, with the bottom of the curve at approximately 2.0 g/kg; the odds ratio (95% CI) was 1.39 (1.36-1.42) for 1.8 g/kg and 8.95 (8.15-9.83) for 2.4 g/kg with reference to 2.0 g/kg for IVIG resistance. Additionally, IVIG dosage was found to have U-shaped associations with the length of stay and medical costs, with the bottom of the curve at approximately 2 g/kg.   Conclusions: IVIG with a dose of 2 g/kg was considered appropriate for the initial treatment of KD. What is Known: • For treatments of acute Kawasaki Disease (KD), IVIG has been the most recommended to reduce fever early and prevent complications of CAAs. Few studies have shown the most effective dosage of IVIG to be administered to prevent CAAs. What is New: • 2 g/kg intravenous immunoglobulin was considered appropriate for the initial treatment of Kawasaki disease.

Clinical Features of Kawasaki Disease With Atlantoaxial Rotatory Fixation.

PURPOSE: Atlantoaxial rotatory fixation (AARF) is a rare complication of acute Kawasaki disease (KD). Early diagnosis and intervention are important for AARF because delayed diagnoses may incur neurological sequelae. However, previous studies on AARF associated with KD are limited, and its clinical characteristics and course are unknown. This study aimed to examine the clinical features and treatment course of KD with AARF using a Japanese national inpatient database. METHODS: Using the Diagnosis Procedure Combination database, we identified KD patients who received intravenous immunoglobulin (IVIG) treatment between July 2010 and March 2020. The clinical characteristics of KD patients with AARF and their risk factors were evaluated using multivariable logistic regression analysis. We also examined the relationship between AARF, the proportion of coronary artery abnormalities (CAAs), IVIG resistance, length of stay and medical costs. RESULTS: We identified 71,913 patients with KD, 166 of whom had AARF. The AARF group had older age, heavier bodyweight and atypical KD. In multivariable analysis, AARF was associated with older age [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.19-1.29], lower body mass index (OR: 0.89; 95% CI: 0.82-0.96) and atypical KD (OR: 1.95; 95% CI: 1.12-3.40). AARF was not associated with CAAs (OR: 0.73; 95% CI, 0.23-2.32) and IVIG resistance (OR: 1.05; 95% CI, 0.74-1.49). However, AARF was associated with higher medical costs (difference, US$1064; 95% CI: 346-1781) and longer hospital stay (difference, 3.1 days; 95% CI: 1.7-4.4). CONCLUSION: AARF in patients with acute KD should be considered if cervical symptoms present in older patients with atypical KD.

An atypical case of Kawasaki disease with severe pneumonia in a neonate.

BACKGROUND: Kawasaki disease (KD) is an acute, febrile, systemic vasculitis of unknown etiology that primarily affects the coronary arteries and generally occurs at around 1 year of age. Although the diagnosis of KD is generally not difficult, it is challenging in cases of incomplete KD lacking characteristic clinical manifestations. The incidence of incomplete KD is higher in infants younger than 6 months of age. Pneumonia is an extremely rare complication of KD and can be misinterpreted as atypical pneumonia rather than KD. Herein, we report a neonate with atypical KD and severe pneumonia who required mechanical ventilation. CASE PRESENTATION: Japanese one-month-old infant had only fever and rash on admission (day 1), and he was transferred to the intensive care unit for severe pneumonia on day 2. Although pneumonia improved following intensive care, he was diagnosed with KD on day 14 because of emerging typical clinical manifestations such as fever, bulbar nonexudative conjunctival injection, desquamation of the fingers, and coronary artery aneurysm. KD symptoms improved after three doses of intravenous immunoglobulin plus cyclosporine. However, small coronary aneurysms were present at the time of discharge. In a retrospective analysis, no pathogens were detected by multiplex real-time PCR in samples collected at admission, and the serum cytokine profile demonstrated prominent elevation of IL-6 as well as elevation of neopterin, sTNF-RI, and sTNF-RII, which suggested KD. CONCLUSIONS: The patient's entire clinical course, including the severe pneumonia, was caused by KD. As in this case, neonatal KD may exhibit atypical manifestations such as severe pneumonia requiring mechanical ventilation.

Eosinophilic granulomatosis with polyangiitis exhibits T cell activation and IgG4 immune response in the tissue; comparison with IgG4-related disease.

OBJECTIVE: To study the pathophysiological differences of EGPA and IgG4-related disease (RD) by clarifying their clinical, pathological and immunological features. METHODS: Clinical and pathological findings were compared in patients with EGPA and IgG4-RD. Peripheral blood mononuclear cells were used for comprehensive flow cytometric analysis. RESULTS: An elevation of the IgG4 level was found in all EGPA cases, with the accompanying pathological findings of lymphocytic infiltration and fibrosis observed in 30.8% patients, and the elevation of IgG4/IgG ratio in 61.5% patients. However, actual IgG4 levels, as well as the degree of the infiltration of IgG4-positive plasma cells, were still higher in patients with IgG4-RD than patients with EGPA. Examination by ACR/EULAR classification criteria showed only 13.6% of the EGPA patients met entry criteria, while all of them met the exclusion criteria. In regard to the immunophenotyping, EGPA patients had increases in activated CD4 and CD8 T cells compared with the healthy controls. However, no such similar changes occurred in IgG4-RD patients. On the other hand, both the EGPA and IgG4-RD patient groups had correlated increased plasmablasts and Tfh. These results indicate the presence of two axes: namely, the activation of T cells and that of B cells. Both axes are present in EGPA, but the T cell activation axis was not observed in IgG4-RD. CONCLUSIONS: The elevation of serum IgG4 as well as pathological IgG4 infiltration are not specific. Meanwhile, EGPA and IgG4-RD differ in immunological phenotypes, indicating the possible importance of the predominant activation of T cells in the development of vasculitis.

Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD.

OBJECTIVE: MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC). METHODS: Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n = 40), SSc (n = 70) and IIM (n = 50)]. RESULTS: All MCTD patients presented Raynaud's phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients. CONCLUSIONS: MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD.

Low- versus high-concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase.

PURPOSE: Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low- and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan. METHOD: We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high- and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score-matched analyses were conducted to compare the outcomes between the 2 groups. Instrumental variable analyses were performed to confirm the results. RESULT: We identified 48 046 patients with KD and created 4:1 propensity score-matched pairs between the low- and high-concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the 2 groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3-4.7]; P < .001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, -0.34 to 0.37]; P = .953). The instrumental variable analyses showed similar results. CONCLUSIONS: The proportion of CAAs did not differ significantly between those receiving low- and high-concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.

Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.

OBJECTIVE: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. METHODS: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) <3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) <2.6 at year 1 and 2, respectively. RESULTS: Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) <2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) <2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group. CONCLUSIONS: After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.