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Background Although there is increasing use of 18F-FDG PET/CT in the diagnostic procedure for IgG4-related disease (IgG4-RD), little is known about the quantification of 18F-FDG PET/CT. We aimed to evaluate the utility of the quantification of 18F-FDG PET/CT in the diagnosis of IgG4-RD by analyzing the relation between 18F-FDG PET/CT findings and histopathologic findings. Methods Twenty-one patients with IgG4-RD, in whom 18F-FDG PET/CT was performed at the time of diagnosis between November 2011 and July 2018, were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardized uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. Results The mean age at diagnosis was 64.6 ± 11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue than those in the histopathology-negative tissue (4.98 and 3.54, respectively P mean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively P mean to determine which of multiple lesions should be biopsied, a receiver operating characteristic (ROC) curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver = 1.66 as a cut-off value that could discriminate IgG4-RD-related lesions. Conclusions Our present study suggested that quantitative analysis of 18FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.

This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments.This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups.All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders.Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.

Objectives: Using multicentre ultrasound (US) cohort data among patients with rheumatoid arthritis (RA), we aimed to identify baseline factors that permit differentiation between two patient cohort...

Objective: To determine whether the positivity of baseline anti-Ro/Sjögren’s syndrome antigen A (SSA) antibodies influences the response to abatacept, we compared therapeutic responses between anti-Ro/SSA antibody-negative and -positive patients with rheumatoid arthritis (RA) using a multicentre RA ultrasonography prospective cohort. Method: We reviewed Japanese patients with RA who started abatacept as the first biological disease-modifying anti-rheumatic drug between June 2013 and April 2018. We assessed 28-joint Disease Activity Score–erythrocyte sedimentation rate (DAS28-ESR) change between baseline and 6 or 12 months after treatment in RA patients treated with abatacept, and European League Against Rheumatism (EULAR) response at 6 and 12 months. The Global OMERACT-EULAR Synovitis Score (GLOESS) was calculated at baseline and at 6 and 12 months. Results: Overall, 51 patients were enrolled and divided into anti-Ro/SSA antibody-negative and -positive groups of 35 and 16, respectively. Median age at baseline was significantly higher in the anti-Ro/SSA antibody-negative group (p = 0.04). The retention rate and percentage of EULAR good responders at 12 months were significantly higher in the anti-Ro/SSA antibody-negative group (both p = 0.02). Anti-Ro/SSA antibody-negative patients exhibited larger decreases in both DAS28-ESR and DAS28-C-reactive protein at 12 months than anti-Ro/SSA antibody-positive patients (p = 0.02 and 0.04, respectively). GLOESS decreased significantly at 6 months in anti-Ro/SSA antibody-negative patients (p = 0.03). Multivariate analyses showed that anti-Ro/SSA antibody positivity was an independent factor associated with change in the DAS28-ESR at 6 months (p Conclusion: Anti-Ro/SSA antibody positivity predicts a poor response to abatacept and low retention rate.

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p

A 54-year-old woman developed drop head syndrome (DHS), Raynaud's phenomenon and creatine kinase (CK) elevation. She did not meet the international classification criteria of dermatomyositis/polymyositis, as we observed no muscle weakness, grasping pain or electromyography abnormality in her limbs, and antiaminoacyl tRNA synthetase (ARS) antibody was negative. Cervical magnetic resonance imaging and a muscle biopsy of the trapezius muscle revealed myositis findings as the only clinical observations in muscle. These findings, along with her anti-U1-ribonucleoprotein (RNP) antibody positivity and leukopenia, resulted in a diagnosis of mixed connective tissue disease (MCTD). Prednisolone treatment significantly improved her myositis. To our knowledge, this is the first report of DHS as the only muscle complication of MCTD., Internal medicine, 59(5), pp.729-732; 2020

We aimed to investigate the effect of methotrexate (MTX) on microRNA modulation in rheumatoid arthritis fibroblast-like synovial cells (RA-FLS). RA-FLS were treated with MTX for 48 h. We then performed miRNA array analysis to investigate differentially expressed miRNAs. Transfection with miR-877-3p precursor and inhibitor were used to investigate the functional role of miR-877-3p in RA-FLS. Gene ontology analysis was used to investigate the cellular processes involving miR-877-3p. The production of cytokines/chemokines was screened by multiplex cytokine/chemokine bead assay and confirmed by ELISA and quantitative real-time PCR. The migratory and proliferative activities of RA-FLS were analyzed by wound healing assay and MKI-67 expression. MTX treatment altered the expression of 13 miRNAs (seven were upregulated and six were downregulated). Among them, quantitative real-time PCR confirmed that miR-877-3p was upregulated in response to MTX (1.79 ± 0.46-fold, p < 0.05). The possible target genes of miR-877-3p in RA-FLS revealed by the microarray analysis were correlated with biological processes. The overexpression of miR-877-3p decreased the production of GM-CSF and CCL3, and the overexpression of miR-877-3p inhibited migratory and proliferative activity. MTX altered the miR-877-3p expression on RA-FLS, and this alteration of miR-877-3p attenuated the abundant production of cytokines/chemokines and proliferative property of RA-FLS., International Journal of Molecular Sciences, 22(21), art. no. 11561; 2021

A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. We suspected familial Mediterranean fever (FMF) based on his history and administered colchicine; his symptoms subsequently improved. Thus, he was diagnosed with atypical FMF. After tocilizumab administration, the amyloid deposits disappeared. This case suggests that physicians should consider FMF even in cases with atypical symptoms in order to prevent the progression of amyloidosis and that amyloid deposits can be eliminated by interleukin (IL)-6 inhibition., Internal Medicine, 58(12), pp.1781-1785; 2019

A 70-year-old woman presented with a fever and pain in both lower extremities and the right shoulder and right upper arm continuously for approximately 3 months. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG/PET-CT) revealed the accumulation of FDG in the right shoulder, lumbar spinous processes, both ischial tuberosities, and both hips and greater trochanters, indicating polymyalgia rheumatica (PMR). In addition, upper gastrointestinal endoscopy revealed esophageal carcinoma. After endoscopic submucosal dissection was performed, her musculoskeletal symptoms spontaneously improved, and the 18F-FDG/PET-CT findings decreased. In light of these findings, she was diagnosed with paraneoplastic syndrome. When atypical features of PMR, such as asymmetric symptoms occur, we should search for malignancies.

BackgroundLupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE).MethodsWe retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993–2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares.ResultsOf the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5–154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44–0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06–0.74, p = 0.00098) levels.ConclusionsAmong LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. Methods: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. Results: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings., Arthritis Research and Therapy, 23, art. no. 197; 2021

BACKGROUND: Most patients with systemic lupus erythematosus (SLE) progress to lupus nephritis (LN) within 5?years of their SLE diagnosis, although it is not uncommon for LN to develop at later time points. Here we evaluated the clinical features of early- and late-onset LN. PATIENTS AND METHODS: We retrospectively analyzed the cases of 184 of the 201 patients who underwent a renal biopsy at Nagasaki University Hospital and associated community hospitals between 1990 and 2016 and were diagnosed as having LN. Early onset was defined as the development of LN within the first 5?years after the patient's SLE diagnosis, and late onset was defined as LN development >?5?years post-diagnosis. We analyzed the complete renal response (CR) at 6 and 12?months after induction therapy, the classification of renal pathology, and the mortality of the early- and late-onset LN groups. RESULTS: The mean follow-up duration after the renal biopsy was 123?±?85?months. There were 113 (61.4%) early-onset patients and 71 (38.6%) late-onset patients. A multivariate analysis revealed that the following factors were predictive of CR: at 6?months: female sex (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.31-11.77, p?=?0.010), proteinuria (OR 0.83, 95% CI 0.71-0.97, p?=?0.009), index of activity (0-24) (OR 0.83, 95% CI 0.70-0.99, p?=?0.030), and early-onset LN (OR 2.39, 95% CI 1.15-4.98, p?=?0.018); at 12?months: female sex (OR 3.60, 95% CI 1.32-9.83, p?=?0.013), mixed LN (OR 0.18, 95% CI 0.04-0.80, p?=?0.024), index of activity (0-24) (OR 0.80, 95% CI 0.68-0.94, p?=?0.007), and early-onset LN (OR 2.10, 95% CI 1.05-4.23, p?=?0.035). In a Cox proportional hazards and Fine-Gray regression model, the early-onset LN group had a significantly better mortality rate than the late-onset LN group (p?=?0.038 and p?=?0.043, respectively). CONCLUSIONS: In our cohort, early-onset LN was a better predictor of CR at 6 and 12?months than late-onset LN. Our results suggest that early-onset LN patients had lower mortality than late-onset LN patients., Arthritis research & therapy, 22(1), art.no.175; 2020

A healthy 32-year-old man had a fever and elevated levels of white blood cells (WBC) and C-reactive protein (CRP). In addition, he presented with a skin rash on his forehead, around the neck, and from the anterior chest to the abdomen. His laboratory findings showed elevated levels of hepatic enzyme, CRP, and ferritin; therefore, he was suspected to have adult-onset Still's disease (AOSD) and referred to our department. We ruled out hematological malignancy and established diagnosis of AOSD according to Yamaguchi’s criteria and treated with 20 mg/day prednisolone. His clinical condition did not improve, therefore, we increased the dosage of prednisolone to 40 mg/day; however, his rash gradually expanded with papules and plaques. A cervical skin biopsy revealed neutrophil dermatosis and analysis of the MEFV gene revealed a heterozygous variant in exon 2 (E148Q). We found an elevated percentage of CD86+CD14+CD16– classical monocytes in the peripheral blood using flow cytometry. We added oral potassium iodide as a treatment for neutrophil dermatosis. Despite this treatment, his eruption and fever did not subside, therefore, we changed potassium iodide to colchicine, this improved his clinical condition. This case suggests the importance of autoinflammation-related gene abnormalities and macrophage activation in the pathogenesis of neutrophil dermatosis.

Background Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. Objectives To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. Methods In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. Results The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. Conclusion This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.

Objectives To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). Methods Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. Results Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. Conclusion This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA.

OBJECTIVES We investigated the impact of renal involvement at diagnosis on the prognosis of patients with antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS The relationship between renal involvement at diagnosis, clinical variables at diagnosis, and prognosis (including relapse episodes, initiation of dialysis, and death) was examined in 101 Japanese patients with AAV. RESULTS Sixty-eight patients had renal involvement at diagnosis. The renal-involvement patients had significantly higher ages at diagnosis, significantly lower hemoglobin levels, and significantly lower platelet levels. They had significantly lower C3 levels, but showed no significant difference in C4 levels. Overall survival rate was significantly worse in patients with than in patients without renal involvement (P = 0.003, log-rank test). Multivariable analysis using a logistic regression model demonstrated that C3 contributed to dialysis initiation: odds ratio (per 10 mg/dL of C3): 0.68; range: 0.49-0.90; P = 0.007. A Cox proportional hazard model revealed that the C3 level and age at diagnosis contributed significantly to overall survival: hazard ratio (per 10 mg/dL of C3) 0.81, range 0.69-0.95, P = 0.011; 1.08, 1.02-1.15, P = 0.013, respectively. Renal involvement did not contribute significantly to overall survival. Patients with C3 levels ≥100 mg/dL had a better survival rate than patients with C3 levels

To assess the efficacy and safety of switching to infliximab (IFX) from other biological disease-modifying anti-rheumatic drugs (bDMARDs) among Japanese patients with rheumatoid arthritis (RA) in daily practice. We examined 24 consecutive RA patients who had not achieved low disease activity (LDA) as the disease activity score-28 for rheumatoid arthritis with erythrocyte sedimentation rate (DAS28-ESR) despite previous bDMARD therapy in this cohort study. We attempted to determine predictive variables that are associated with achieving DAS28-ESR LDA at 22 weeks post-IFX introduction, by performing univariate analysis. The median DAS28-ESR at baseline was 5.41. Sixteen patients (66.7%) had been treated with a tumor necrosis factor inhibitor (TNF-i), and the other eight patients (33.3%) received a non-TNF-i (abatacept or tocilizumab). Nine patients (37.5%) achieved LDA or remission at 22 weeks. Univariate analyses showed that the variable to predict LDA achievement at 22 weeks was tender joints (>8 counts) at baseline (adjusted odds ratio, 0.10; 95% confidence interval, 0.01-0.63; p = .02). Nine adverse events were observed during the study period, and infection requiring hospitalization was observed in one patient. Switching to IFX is effective to achieve LDA or remission for RA patients refractory to bDMARDs.

A 44-year-old Japanese man with a 14-year history of limited cutaneous systemic sclerosis (SSc) was admitted with a fever, hypertension, anemia, thrombocytopenia, and renal dysfunction. On admission, hypertension, hyperreninemia, acute renal dysfunction,hemolytic anemia, and thrombocytopenia led to the diagnosis of scleroderma renal crisis (SRC) complicated with thrombotic microangiopathy (TMA). The patient had also been infected with influenza B virus almost six days before admission. Following treatment with plasma exchange,an angiotensin-converting enzyme inhibitor, and an anti-virus agent, his general condition improved. He had no risk factors for SRC.In SSc patients, an influenza virus infection might trigger SRC complicated with TMA., Internal medicine, 58(3), pp.441-445; 2019

A 70-year-old Japanese woman presented to our hospital with gait disturbance and cognitive dysfunction. Since she had arthritis, lymphopenia, hypocomplementemia, and anti-nuclear and anti-double-stranded DNA antibodies, she was diagnosed with systemic lupus erythematosus (SLE). T2-weighted magnetic resonance imaging revealed bilateral hyperintensities in the putamen. Based on her cognitive impairment, muscle rigidity, and high levels of interleukin-6 in the cerebrospinal fluid, we believed she had developed a complication of a neuropsychiatric disease and administered corticosteroids and intravenous cyclophosphamide therapy. Her cognitive function fully recovered, and her gait disturbance improved. Attending to cognitive impairment in elderly SLE patients is necessary., Internal medicine, 57(20), pp.3025-3028; 2018

The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4+CD52hi T cells are functioning suppressor CD4+T cells. We investigated the role of the immune regulation of CD4+CD52 T cells in systemic lupus erythematosus (SLE). CD4+CD52lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4+CD52lo T cells. Chemokine receptor 8 (CCR8) expression in CD4+CD52lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4+CD52hi T cells into CD4+CD52lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4+CD52lo T cells.

Rationale: The pathology of gouty arthritis and reactive arthritis (ReA) partially overlaps, and both diseases are characterized by the production of inflammatory cytokines associated with the activation of monocytes and macrophages. However, the precise cytokine profile of cases with a coexistence of both diseases is unknown, and there are few reports on the course of treatment in patients with both gouty arthritis and ReA. Patient concerns: A 39-year-old man with a recurrent episode of gouty arthritis presented prednisolone-resistant polyarthritis with high level of C-reactive protein (CRP). He had the features of gouty arthritis such as active synovitis of the first manifestation of metatarsophalangeal (MTP) joints and the presence of monosodium urate (MSU) crystals from synovial fluid. But he also had the features of ReA such as the presence of tenosynovitis in the upper limb, the positivity of human leukocyte antigen (HLA)-B27, a history of sexual contact and positive findings of anti-Chlamydia trachomatis-specific IgA and IgG serum antibodies. Diagnoses: He was diagnosed with HLA-B27 associated Chlamydia-induced ReA accompanied by gout flares. Interventions: He was treated with 180 mg/day of loxoprofen, 1 mg/day of colchicine, and 10 mg/day of prednisolone for gout flares. However, his polyarthritis worsened with an increased level of CRP (23.16 mg/dL). Accordingly, we added 500 mg/day of salazosulfapyridine followed by adalimumab (ADA) 40 mg once every 2 weeks. Outcomes: After starting ADA, the patient's symptoms and laboratory findings showed rapid improvement and he achieved clinical remission 1 month after initiation of ADA treatment. As of this writing, the patient's clinical remission has been maintained for >1 year. Lessons: This case suggests that with exacerbation of arthritis during gouty arthritis, coexistence with other pathologies such as peripheral spondyloarthritis should be considered, and early intensive treatment including tumor necrosis factor inhibitors may be necessary.

Background The antimalarial drug hydroxychloroquine (HCQ) is used worldwide to control the disease activity of systemic lupus erythematosus (SLE). In Japan, HCQ was not approved until September 2015 due to the problem of retinopathy induced by chloroquine. There is insufficient evidence of the effects of HCQ or adverse events linked to HCQ treatment. Objectives Here, we evaluated adverse events and the relapse risk of SLE during HCQ treatment. Methods We retrospectively analyzed the data of 109 patients diagnosed with SLE and treated with HCQ for ≥12 months at Nagasaki University Hospital and community hospitals. The demographic data included the patient‘s age at the onset of SLE, gender, the disease duration of SLE (the time from the diagnosis of SLE until the renal biopsy), comorbidities of Sjogren syndrome (SS)/anti-phospholipid syndrome (APS), and the treatment for induction. We identified the risk of adverse events and relapse at 12 months after the introduction of HCQ. Decision tree models predicting relapse were built with the Classification and Regression Trees (CART) algorithm. The data of the length of time between a patient‘s HCQ induction to the first observation of relapse was analyzed by the Kaplan-Meier method with a log-rank test. Results Most of the patients were female (88.1%). The median age at the introduction of HCQ was 40.0 years (interquartile range [IQR] 30.5–50.0 years), and the SLE disease duration was 95 months (IQR 38.0–184.5 months). The mean observation period after HCQ introduction was 12 months. The comorbidity rates of SS and APS were 25.7% and 20.2%, respectively. The SELENA-SLEDAI scores were significantly decreased at 3 months post-HCQ introduction. The dose of oral prednisolone was significantly decreased at 6 months post-HCQ introduction. Eighty-six patients (78.9%) were continuing HCQ at 12 months post-introduction. Adverse events occurred in 27 patients (24.8%), including skin rashes (n=11, 10.1%) and gastrointestinal symptoms (n=6, 5.5%). The sole predictive factor for adverse events was the white blood cell (WBC) count at baseline (odds ratio: 0.9997, 95%CI: 0.9994–0.9999, p=0.0285). Twelve of 86 patients (14.0%) experienced relapse that required the start of prednisolone or an immunosuppressant or an increased prednisolone dose. The multivariate analysis revealed that the C4 value at baseline was a predictive factor of relapse (odds ratio: 0.841, 95%CI: 0.718–0.984, p=0.0097). The cut-off point determined by the CART algorithm showed that C4 ≥9.3 mg/dl at baseline provides the best performance for predicting relapse. The Kaplan-Meier analysis showed that compared to C4 Conclusion A lower C4 value at HCQ introduction was a predictive factor for the relapse of SLE, and a lower WBC count was a predictive factor for adverse events. References [1] Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017 Mar;16(3):411-419. doi: 10.1080/14740338.2017.1269168. Disclosure of Interests None declared

Background Systemic lupus erythematosus (SLE) is multisystem disorder that is caused by tissue damage resulting from antibody and complement-fixing immune complex deposition. Lupus nephritis (LN) is frequent complication and one of the most serious manifestations of SLE. The expression of nephrin, as podocyte marker, is reduced in various renal diseases that develop into nephrotic syndrome1). The alteration of the structural protein in podocytes is known as a mechanism of proteinuria in LN. Objectives The signaling lymphocyte activation molecule family (the SLAM family) of type I transmembrane receptors consists of nine related members of the immunoglobulin superfamily and has been reported to mediate important regulatory signals between immune cells through their homophilic and heterophilic interactions2).The 1q23 region (Sle1b region in mouse) on human chromosome 1 including the SLAMF cluster of genes, containing SLAMF6 has been identified as a lupus susceptibility locus3).It has been shown that the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) is enhanced in CD4+T cells of SLE patients and is involved in IL-17 production4). We sought to examine the functional role of SLAMF6 in lupus podocytes. Methods We evaluated the co-expression of nephrin, a podocyte marker and SLAMF6 in kidney of normal controls and LN patients, also in B6 and MRL/lpr mice at the age of 8wk and 16wk by immunofluorescence analysis. We also examined nephrin positive SLAMF6 expression in isolated podocytes from B6 and MRL/lpr kidneys. Then, we analyzed the expression of SLAMF6 in CD4+T cells of isolated kidney and spleen in B6 and MRL/lpr mice. We treated human podocytes with IgG from healthy individuals and LN patients for 24 h and 48h and analyzed the expression of SLAMF6 by real-time PCR. Results In the histopathology, the expression of SLAMF6 was increased in nephrin positive area in LN patients and MRL/lpr mice compared to each control groups. Although the expression of nephrin in MRL/lpr mice kidney at 16 wk old decreased compared to B6 mice at same age, the expression of SLAMF6 in podocytes increased in diseased MRL/lpr mice compared to B6 mice. Similarly, the expression of SLAMF6 in CD4+ T cells increased in diseased MRL/lpr mice kidney and spleen compared to B6 mice. The level of SLAMF6 mRNA elevated in human podocytes exposed to LN-derived IgG compared to healthy individuals-derived IgG. Conclusion The expression of SLAMF6 is enhanced in LN podocytes, suggesting that the possibility of cooperating with CD4+T cells contributing to its dysfunction. Further examination is needed to investigate in detail how SLAMF6 is involved in the development of LN in the future. References [1] J Am Soc Nephrol. 2003Aug;14(8):2063-71., [2] Nat Rev Immunol. 2003Oct;3(10):813-21., [3] Nat Rev Rheumatol. 2010Jun;6(6):348-57., [4] J Immunol2012; 188:1206-1212. Disclosure of Interests Takashi Igawa: None declared, Kunihiro Ichinose: None declared, Mizuna Eguchi: None declared, Momoko Okamoto: None declared, Yushiro Endo: None declared, Sousuke Tsuji: None declared, Ayuko Takatani: None declared, Toshimasa Shimizu: None declared, Remi Sumiyoshi: None declared, Tomohiro Koga: None declared, Shin-ya Kawashiri: None declared, Naoki Iwamoto: None declared, Mami Tamai: None declared, Hideki Nakamura: None declared, Tomoki Origuchi: None declared, Atsushi Kawakami Grant/research support from: Astellas Pharma, Consultant for: Astellas Pharma, Speakers bureau: Astellas Pharma

Background The antimalarial drug hydroxychloroquine (HCQ) has been widely used in the world to control the disease activity of systemic lupus erythematosus(SLE). In Japan, it has not been approved until September 2015 due to the problem of retinopathy induced by chloroquine. For these reasons, there is insufficient evidence for its effects and adverse events. Here, we evaluated adverse events and relapse risk of SLE during the treatment of HCQ. Methods We conducted an analysis of retrospectively collected data of 109 patients who were diagnosed as SLE and treated with HCQ at least 12 months at Nagasaki University Hospital and community hospitals. Demographic data included the patient‘s age at the onset of SLE, gender, the disease duration of SLE (the time from the diagnosis of SLE until the renal biopsy), comorbidities of Sjogren syndrome (SS)/anti-phospholipid syndrome (APS), and the treatment for induction. We identified the risk of adverse events and relapse at 12 months after introduction of HCQ. Results Most of the patients were female (88.1%). The median age at introduction of HCQ was 40.0 years (interquartile range [IQR] 30.550.0 years), and the disease duration of SLE was 95 months (IQR 38.0184.5 months). The mean observation period after HCQ introduction was 12 months. The comorbidity rates of SS and APS were 25.7% and 20.2%, respectively. The SELENA-SLEDAI decreased significantly after 3 months of introduction. The dose of oral prednisolone also decreased significantly after 6 months of introduction. Eighty-six cases (78.9%) continued HCQ at 12 months after introduction. The adverse events appeared in 27 cases (24.8%), including 11 cases of skin rashes (10.1%) and 6 cases of gastrointestinal symptoms (5.5%). Predictive factor for adverse event was white blood cell (WBC) counts at baseline (odds ratio: 0.9997, 95% CI: 0.9994–0.9999, p=0.0285). Twelve of 86 cases (14.0%) experienced relapse those who needs to start prednisolone/immunosuppressants or increase the dose of prednisolone. The multivariate analysis revealed C4 value at baseline was the predictive factor of relapse (odds ratio: 0.841, 95% CI: 0.718–0.984, p=0.0097). Conclusions We retrospectively analyzed the risk of adverse events and relapse after HCQ introduction with a mean 12 month follow-up in SLE. The lower value of C4 at HCQ introduction was a predictive factor for relapse and the lower counts of WBC was a predictive factor for adverse event. Funding Source(s): N/A

Background:Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, which results in reduced secretory functions and oral and ocular dryness (1). In addition, patients often have extraglandular manifestations, such as interstitial pneumonia and interstitial nephritis, and the appearance of autoantibodies such as anti-Ro/SS-A and La/SS-B antibodies. Salivary gland ultrasonography (SGUS) is typically used to evaluate the findings of salivary glands; thus, we can evaluate the severity of salivary gland disorders due to SS using SGUS in real time (2).Objectives:To identify clinical indices, including disease activity, associated with glandular involvement evaluated using SGUS in patients with SS.Methods:We enrolled patients with SS (n=115) and non-SS sicca subjects (n=90) who visited Nagasaki University Hospital between 1995 and 2019. The patients’ SS classifications were based on the 2002 American–European Consensus Group (AECG) SS classification criteria (3). The non-SS sicca subjects exhibited sicca symptoms but did not fulfill the AECG SS classification criteria. SGUS and clinical indices such as age, sex, the focus score (FS), sicca symptoms, the Saxon test results, Schirmer’s test results, anti-SS-A/Ro antibody positivity, anti-SS-B/La antibody positivity, anti-centromere antibody (ACA) positivity, serum immunoglobulin G levels, and the clinical European League Against Rheumatism SS disease activity index were examined. The ultrasonography (US) score was calculated based on SGUS imaging (hypoechoic area, hyperechoic band, and irregular border) (4).Results:The US score was significantly higher in patients with SS than that in non-SS sicca subjects. In addition, we found significant correlations between the US score and FS in patients with SS. Multivariate analysis revealed the FS, Saxon test positivity, and ACA positivity as the variables independently associated with the US score in patients with SS. These results were the same in the primary SS patient group (n=96). Patients with ACA positivity had significantly higher US scores compared to those in patients with ACA negativity, whereas the FS was not significantly high. In addition, patients with ACA positivity had significantly greater positivity of hyperechoic bands than that in patients with ACA negativity.Conclusion:This study indicated that ACA positivity, which is not reflected in sialadenitis of SS, is associated with the US score in patients with SS. These results suggest that US findings of patients with ACA positivity might show specific changes in salivary glands, such as fibrosis, and not only sialadenitis (5).References:[1]Ramos-Casals M, Tzioufas AG, Font J. Primary Sjogren’s syndrome: new clinical and therapeutic concepts. Ann Rheum Dis. 2005;64(3):347-54.[2]van Ginkel MS, Glaudemans A, van der Vegt B, Mossel E, Kroese FGM, Bootsma H, et al. Imaging in Primary Sjogren’s Syndrome. J Clin Med. 2020;9(8).[3]Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554-8.[4]Takagi Y, Nakamura H, Sumi M, Shimizu T, Hirai Y, Horai Y, et al. Combined classification system based on ACR/EULAR and ultrasonographic scores for improving the diagnosis of Sjogren’s syndrome. PLoS One. 2018;13(4):e0195113.[5]Nakamura H, Kawakami A, Hayashi T, Iwamoto N, Okada A, Tamai M, et al. Anti-centromere antibody-seropositive Sjögren’s syndrome differs from conventional subgroup in clinical and pathological study. BMC Musculoskelet Disord. 2010;11:140.Disclosure of Interests:None declared

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs., Medicine, 100(1), e23254; 2021

Background:Cardiovascular disease(CVD) has been identified as a major cause of morbidity and mortality in patients with lupus nephritis(LN)1) 2). There is a clear causal relationship between the onset of neonatal lupus (cardiac complications) and SS-A antibodies3) 4), but no association has been reported in adults. In recent years, there have been reports from overseas that suggest the association between CVD and anti-SS-A antibody in adult systemic lupus erythematosus (SLE) patients5) 6). So far, no studies have not been reported to evaluate the relationship between anti-SS-A antibody and the risk of developing CVD in LN in a large cohort of patients with SLE in Japan.Objectives:The aim of this study was to evaluate the association between anti-SS-A antibody and the risk of developing CVD in LN patients using a multicenter registration study [Lupus registry of nationwide institution (LUNA)] in Japan.Methods:We identified 931 patients diagnosed with SLE in the Lupus registry of nationwide institution (LUNA), and further identified 275 LN patients with known the presence or absence of both development of CVD and presence of anti-SS-A antibody. We defined the exposure factor as anti-SS-A antibody, and the outcome as CVD. SELENA-SLEDAI score (at diagnosis), eGFR Results:We found 68 patients (24.7%) complicated with CVD, including percarditis (7.3%), cerebrovascular disorder (6.2%), peripheral Arterial Disease (6.2%), Ischemic heart disease (2.9%),venous thromboembolism (2.9%),pulmonary hypertension (1.5%), vulvular heart disease (1.1%), and cardiomyopathy (0.4%). In univariate analysis, there was no significant difference in the occurrence of CVD depending on the presence or absence of anti-SS-A antibody (p = 0.32), and the results of multivariate analysis showed no significant difference in anti-SS-A antibody [p = 0.23, odds: 0.41, 95% confidence interval (0.09-1.89)].Conclusion:The association between anti-SS-A antibody and the development of CVD in LN patients in Japan has not been identified.References:[1]Lupus. 2000;9(3):166-9[2]Arthritis Rheum.2019 Mar;71(3):403-410,[3]J Intern Med 265:653-662, 2009[4]Nat Clin Pract Rheumatol 5:139-148, 2009[5]Ann Rheum Dis 1990;49:627-629[6]Chest. 2018 Jan;153(1):143-151. Doi:Disclosure of Interests:None declared

Background:It has been reported that the incidence of cancer in patients with systemic lupus erythematosus (SLE) is higher than that in healthy individuals, but the findings are inconsistent1. In the transplantation field, a few studies indicated an association between the use of immunosuppressants and an increased risk of cancer2. Calcineurin inhibitors (CNIs), which include cyclosporine and tacrolimus, have been used for >30 years to treat renal and extrarenal manifestations of SLE, but the effects of exposure to CNIs among SLE patients have not been established.Objectives:We investigated the incidence of various cancers (including cervical dysplasia) among SLE patients registered in the LUpus registry of NAtionwide institution (LUNA). We also investigate whether the registrants’ exposure to CNIs increased the risk of cancer.Methods:We calculated the standardized incidence ratio (SIR) of cancer among SLE patients based on the age-standardized incidence rate of cancer reported by Japan’s Ministry of Health, Labour and Welfare. A multivariate analysis of the risk of cancer was performed using the covariates of age, smoking history, CNI treatment history, maximum steroid dose in the past, and Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index [SDI]) value (excluding the occurrence of cancer) at the time of the patient’s registration.Results:We studied 714 patients (663 females; 88.9%).The median age at registry was 44 [interquartile range (IQR): 35–56] years. The median past max. steroid dose was 40 mg/day (IQR: 30–60 mg/day), and the SDI at registration was 1 (IQR 0–2). Smoking history was present in 248 patients (34.9%), and 53 patients (7.4%) experienced cancer complications. Gynecologic malignancies accounted for 71% of all cancers, including 12 cervical dysplasia cases. The standardized incidence rate of cancer in these SLE patients was 1.46 (95%CI: 1.07–1.85, pConclusion:The incidence of cancer in SLE was higher in the LUNA cohort than in the general population. Our results suggest that CNI treatment for individuals with SLE is not a risk factor for the development of cancer.References:[1]Ladouceur A. et.al, Expert Rev Clin Immunol. 2018 Oct;14(10):793-802.[2]Gutierrez-Dalmau A. et.al, Drugs 2007;67(8):1167-98.Disclosure of Interests:None declared

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment. Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation. Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months. Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

High serum concentrations of thymus and activation-regulated chemokine (TARC) are observed in allergic diseases such as atopic dermatitis and bronchial asthma. Frequent allergic symptoms have been reported in patients with IgG4-related disease (IgG4-RD). We investigated the pathogenic role of TARC as a biomarker in IgG4-RD patients. We evaluated the serum concentrations of TARC from 29 IgG4-RD patients, 28 primary Sjogren syndrome (pSS) patients, and 23 healthy controls (HCs) by enzyme-linked immunosorbent assay (ELISA). We analyzed the correlations between the TARC concentrations and the subjects’ clinical parameters. To investigate the biological effect of TARC on the pathogenesis of IgG4-RD, we evaluated the in vitro induction of plasmablasts from IgG4-RD patients by TARC. The serum concentrations of TARC in the IgG4-RD patients were significantly higher than those of the pSS patients and HCs. The serum TARC concentration of the IgG4-RD group was positively correlated with the IgG4-RD responder index (IgG4-RD RI) score and with the number of organs involved, but it was not correlated with the serum IgG4 level or eosinophil number in the IgG4-RD patients’ peripheral blood. The patients who had lung involvement had higher serum TARC concentrations. In vitro, TARC clearly induced the formation of plasmablasts from the IgG4-RD patients’ peripheral blood mononuclear cells. Collectively, our data suggest that a systemic increment of TARC may contribute to the development of IgG4-RD through an aberrant induction of plasmablasts., Scientific reports, 10(1), art.no.6010; 2020

BACKGROUND: We showed previously that Japanese individuals with familial Mediterranean fever (FMF) have a more atypical phenotype compared to endemic areas. The clinical differences between young-onset FMF (YOFMF), adult-onset FMF(AOFMF), and late-onset FMF(LOFMF)in Japan are unclear. METHODS: We enrolled 395 consecutive patients. We defined YOFMF, AOFMF, and LOFMF as the onset of FMF at, Arthritis Research & Therapy, 20(1), 257; 2018

A 56-year-old Japanese woman with muscle weakness, increased creatine kinase and aldolase levels, and characteristic cutaneous lesions was diagnosed with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 antibody)-positive dermatomyositis. She also had interstitial lung disease (ILD). After corticosteroid and tacrolimus combination therapy was started, bicytopenia and elevated serum ferritin and trans-aminase emerged. Because the bone marrow tissues were hypoplastic with hemophagocytes, she was diagnosed with concomitant autoimmune-associated hemophagocytic syndrome (HPS). Intravenous cyclophosphamide pulse therapy and plasmapheresis were performed. The laboratory findings indicated improved abnormalities, and the ILD did not progress. Anti-MDA5 antibody-positive dermatomyositis can be complicated by HPS., Internal Medicine, 57(23), pp.3473-3478; 2018

Rationale: Among all dermatomyositis (DM) patients, antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) positive patients have significantly poor short-term mortality, whereas they experience less relapses over the long term after the remission. We report the case of a patient with anti-MDA5 Ab-positive clinically amyopathic dermatomyositis (CADM) with the recurrence of interstitial lung disease (ILD) after 7 years of remission. There has been no case report of an anti-MDA5 Ab-positive DM patient with the recurrence of ILD after 7 years of long-term remission. Patient concerns: A 70-year-old Japanese woman was diagnosed with anti-MDA5 Ab-positive CADM and ILD. After achieving 7 years long-term remission, she was admitted to our department with erythema on the fingers and interstitial pneumonia. Her anti-MDA5 Ab titer was elevated. Diagnoses: We diagnosed recurrent CADM complicated with ILD. Interventions: We successfully treated her with 1,000 mg of methyl-prednisolone pulse and intravenous cyclophosphamide therapy followed by prednisolone 50 mg/day and an increase of cyclosporine. Outcomes: After that treatment, the patient's skin symptoms and interstitial pneumonia were relieved. All laboratory investigations such as ferritin, the serum markers of interstitial pneumonia (i.e., SP-A, SP-D), and the titer of anti-MDA5 Ab showed signs of improvement. Lessons: Her case suggests that careful physical examinations and monitoring the serum markers are important even after long-term remission is achieved.

Objective To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice. Methods We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy. Results After a mean follow-up of 41 months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01-0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis. Conclusion The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.

We examined the efficacy and safety of denosumab as treatment for glucocorticoid-induced osteoporosis (GIOP) patients complicated with rheumatic diseases, by measuring patients’ lumber bone mineral density (BMD) and bone turnover markers. A total of 66 consecutive patients for whom denosumab was initiated between July 2013 and August 2016 were enrolled and evaluated for 12 months. All of the patients were treated with glucocorticoids for underlying rheumatic diseases. The clinical assessment included measurements of the BMD of the lumbar spine (L2–L4) by a dual-energy X-ray absorptiometry technique and the bone turnover markers N-terminal telopeptide of type 1 collagen (NTX) in urine, serum intact procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) at baseline, 6 months and 12 months after the start of denosumab treatment. Adverse events (AEs) until 12 months were also analyzed. The mean percentage changes in BMD from baseline to 6 and 12 months were significant (2.85% increase, p

Background Magnetic resonance imaging (MRI) and ultrasound (US) are both useful modality to monitor disease status of RA whereas combination analysis of disease course by both modalities are quite few. Objectives To clarify the predictors of radiographic progression in patients with RA examined by both MRI and US. Methods Thirty-three patients with active RA, managed with a treat-to-target strategy and checked disease activity score every three months along with examination of both MRI and US, were enrolled from June 2010 to June 2016 and observed for 12 months. US of wrist and finger joints was examined every three months, MRI and radiograph were done every six months. US were evaluated by synovitis score of semi-quantitative manner by gray-scale (GS) and power Doppler (PD) proposed from EULAR. In MRI, synovitis, bone oedema and bone erosion were assessed by the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). Radiographic bone erosion and joint space narrowing (JSN) were scored by Genant-modified Sharp Score (GSS). Radiographic progression was defined as delta radiographic score >0.5. Multivariate analysis was employed to clarify independent predictors for radiographic progression at 12 month. Results Thirteen patients were treated with methotrexate monotherapy and eighteen were received combination of methotrexate and biologics. Three were given biologic monotherapy. Median of age was 57.0 years and that of disease duration was 9 months. Female was 84.8%, positive rate of RF was 87.1% and that of ACPA was 79.3%. DAS28-CRP was 4.20, total GS score 6.0, total PD score 4.0, MRI synovitis score 6.0, MRI bone oedema score 3.0, MRI bone erosion score 3.0, and GSS score 1.0 at baseline. Radiographic progression was found in 12 patients. Multivariate analysis revealed that high MRI bone oedema score at baseline, high MRI bone oedema score and PD ≧ grade 2 articular synovitis at any joints at 6 month were associated with radiographic progression at 12 months. Clinical indices of DAS28-CRP at any point did not predict radiographic progression compared with MRI or US. Conclusions During treat-to-target strategy, the presence of MRI bone oedema as well as PD ≧ grade 2 articular synovitis are found to be important to predict radiographic outcome in active RA patients. These imaging indices may be more sensitive to monitor radiographic progression as compared with clinical indices. Disclosure of Interest None declared

Background We previously reported that the presence of autoantibodies, magnetic resonance imaging (MRI) bone oedema, ultrasound (US) power Doppler (PD) x grade 2 articular synovitis are indispensable markers to predict the development of RA from undifferentiated arthritis whereas combination analysis used by the above variables, focusing on very early phase of arthritis, remains to be done in our cohort. Objectives To investigate and re-confirm the diagnostic performance of autoantibodies, MRI findings and US findings toward early RA from NAGASAKI EARLY ARTHRITIS COHORT. Methods One hundred and three patients, suffering arthralgia less than 6 months and examined by both MRI and US of wrist and finger joints, were selected from NAGASAKI EARLY ARTHRITIS COHORT dating from September 2009 to August 2017. US were evaluated by synovitis score of semi-quantitative manner by gray-scale (GS) and power Doppler (PD) proposed from EULAR. In MRI, synovitis, bone oedema and bone erosion were assessed by the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). After univariate analysis, multivariate analysis was employed to clarify the diagnostic predictors of early RA. Results Median of age was 60 years and that of symptomatic duration was 2 months. Female was 68.9%, positive rate of RF was 64.7% and that of ACPA was 47.1%. Total GS score was 4.0, total PD score 2.0, MRI synovitis score 3.0, MRI bone oedema score 0, MRI bone erosion score 0. Seventy patients were diagnosed as early RA during follow-up periods. A univariate analysis showed ACPA, CRP, MMP-3, fulfilment of 2010 ACR/EULAR criteria, MRI synovitis score, MRI bone oedema score, total GS score, total PD score and PD x grade 2 articular synovitis were associated with early RA. Multivariate analysis revealed ACPA and PD x grade 2 articular synovitis at any joints were independent predictors toward diagnosis of early RA. Conclusions Our present study re-confirms the importance of ACPA, PD x grade 2 articular synovitis and MRI bone oedema, especially the former two, to predict the development of early RA from undifferentiated arthritis patients. Disclosure of Interest None declared

Background Our previous nation-wide survey showed the clinical manifestations and prevalence of Japanese Familial Mediterranean Fever (FMF) patients. However, the clinical differences between young-onset FMF (YOFMF), adult-onset FMF (AOFMF), and late-onset FMF (LOFMF) have not been yet clarified. Objectives We sought to compare between the clinical profile of patients with AOFMF, LOFMF and YOFMF and to determine the clinical characteristics of them. Methods We enrolled consecutively 395 patients in 2006–2017. Mutation detection in exons 1, 2, 3, and 10 of the MEFV gene was performed. We defined YOFMF, AOFMF and LOFMF as the onset of FMF MEFV gene among these three groups. Results The median age at the onset of YOFMF, AOFMF and LOFMF were 12.5, 28 and 51 years old respectively. A family history of FMF and a mutation in exon 10 of the MEFV gene were significantly more frequent in groups with younger onset ([YOFMF 28%, AOFMF 17%, LOFMF 12%; p Conclusions Our results suggest that older onset FMF had a lower percentage of mutations in exon10 of the MEFV gene and predominantly presented arthritis and muscle pain during the attacks. It is thus important to distinguish them from other inflammatory diseases such as gout, adult Still’s disease, and infectious arthritis. Disclosure of Interest None declared

A 72-year-old Japanese woman diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was admitted to our hospital with hearing loss, temporal pain, and sudden blindness. We finally diagnosed recurrent granulomatosis with polyangiitis and initiated methyl-prednisolone pulse therapy (1,000 mg) followed by prednisolone (30 mg/day) and rituximab (RTX). After the third RTX administration, she developed bloody stools along with acute thrombocytopenia and low complement levels. We diagnosed rituximab-induced acute thrombocytopenia (RIAT), and her platelet counts spontaneously recovered. This case suggests that after RTX therapy RIAT may sometimes cause severe thrombocytopenia, and that monitoring the complements may be useful for making an early diagnosis of RIAT., Internal Medicine, 57(15), pp.2247-2250; 2018

A woman in her thirties was diagnosed as Takayasu's arteritis (TAK) by dilatation, wall thickness of her abdominal aorta in contrast-enhanced computed tomography. Although she didn't have any subjective bowel symptoms, fluorodeoxyglucose (FDG)-positron emission tomography (PET) also revealed uptake of FDG in descending colon, and colonoscopy revealed aphthous colitis. After the start of steroid therapy, both arteritis and colitis were improved. FDG-PET can detect TAK and inflammatory bowel diseases at an early stage. FDG-PET is a less invasive module with a high sensitivity for detecting colitis, therefore should be considered for TAK even without physical colon symptoms.

The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4