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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.

The aim of our study was to analyze the expressions of nuclear factor of activated T cells (NFAT)-related substances including long noncoding RNA NRON which participates in pathophysiology of Sjögren’s syndrome (SS), and to assess the histologic findings in individuals with SS. In this study, the expressions of NRON, NFATc1, CD3/CD4, and proviral integration site for Moloney murine leukemia virus (PIM)-1 were examined by in situ hybridization, immunohistochemical analysis, and immunofluorescence in labial salivary glands (LSGs) obtained from 16 patients with SS and five controls. The microcell count method has been applied to calculate the NFATc1-positive area/infiltrating cell area in LSGs, and we compared those results to the infiltrating cell area, focus score, serum immunoglobulin G, and the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index. The NRON expression in the nuclei of cell-infiltration lesions of the SS patients were prominent. The NFATc1 expression was strong in the cytoplasm of infiltrating mononuclear cells and weak in ducts of both SS and controls. In SS, the NFATc1-positive area/infiltrating cell area was positively correlated with the infiltrating cell area and focus score. CD3/CD4 was expressed in infiltrating mononuclear cells, and PIM-1 colocalized with NFATc1 in the cytoplasm. These results suggest NRON along with NFATc1/PIM-1 in SS LSGs might participate in SS pathophysiology., Applied immunohistochemistry & molecular morphology, 29(10), pp. 734-740; 2021

Background Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. Methods Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD. Results In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. Conclusion Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

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...

A large G4C2-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal degeneration associated with this expansion arises from a loss of C9orf72 protein, the accumulation of RNA foci, the expression of dipeptide repeat (DPR) proteins, or all these factors. We report the discovery of a new targeting sequence that is common to all C9orf72 transcripts but enables preferential knockdown of repeat-containing transcripts in multiple cellular models and C9BAC transgenic mice. We optimize stereopure oligonucleotides that act through this site, and we demonstrate that their preferential activity depends on both backbone stereochemistry and asymmetric wing design. In mice, stereopure oligonucleotides produce durable depletion of pathogenic signatures without disrupting protein expression. These oligonucleotides selectively protect motor neurons harboring C9orf72-expansion mutation from glutamate-induced toxicity. We hypothesize that targeting C9orf72 with stereopure oligonucleotides may be a viable therapeutic approach for the treatment of C9orf72-associated neurodegenerative disorders., C9orf72 expansion mutations are the most common genetic cause of ALS and FTD, which have limited therapies. The authors generate stereopure oligonucleotides that selectively deplete expansion-containing transcripts and protect against expansion-associated pathologies in preclinical models.

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.

A 74-year-old man with interstitial lung disease (ILD) underwent surgical excision of a growing retroperitoneal tumor and was diagnosed with spindle cell sarcoma. Just after the surgery, skin eruption and muscle weakness emerged. Based on his symptoms and examination findings, we diagnosed him with anti-synthetase syndrome (ASS) with positive anti-glycyl-transfer ribonucleic acid synthetase antibody (anti-EJ) as paraneoplastic syndrome. Immunosuppressive treatments kept his progressing ILD stable for 21 months, although an expanding lung metastatic lesion from primary sarcoma was detected. Measurements of myositis-specific antibodies may enable the prediction of the efficacy of immunosuppressive treatments for paraneoplastic syndrome, even if the primary disease becomes progressive., Internal Medicine, 59(16), pp.2071-2076; 2020

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

Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the s-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota., Scientific Reports, 10(1), art.no.9466; 2020

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

Objective: To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis. Method: We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis. Results: Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%). Conclusion: Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines., Arthritis Research and Therapy, 23, art. no. 260; 2021

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

To retrospectively analyze the differences in musculoskeletal ultrasound (MSUS) findings to distinguish patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and patients with elderly-onset rheumatoid arthritis (EORA). We consecutively recruited patients with RS3PE syndrome (n = 7) and EORA (n = 22) who underwent pre-treatment MSUS of both hands. Synovial hypertrophy and vascularity of articular synovitis and those of tenosynovitis of the digital flexor tendons and the carpal extensor tendon were evaluated by gray-scale and power Doppler, respectively on a semi-quantitative scale (0–3). The presence/absence of intra-articular synovial effusion, bone erosion, peritendinitis of the digital extensor tendon, and subcutaneous edema were noted. Compared to the EORA group, mild articular synovitis was observed more extensively, and the frequency of intra-articular synovial effusion was significantly higher in the RS3PE syndrome group. Severe articular synovial hypertrophy was more frequent in the EORA group compared to the RS3PE syndrome group, and bone erosion was observed in some EORA cases. Tenosynovitis of the digital flexor tendon was more frequent and severe in the RS3PE syndrome group compared to the EORA group. Although the frequency and severity of tenosynovitis of the carpal extensor tendon were similar in the two groups, digital extensor tendon peritendinitis was more frequent in the RS3PE syndrome group. To distinguish patients with RS3PE syndrome from those with EORA, it is important to evaluate not only intra-articular lesions but also extra-articular lesions by MSUS.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction characterized by marked hyperplasia of the lining layer of the synovium. Fibroblast-like synovial cells (FLS) is a key cellular component within the synovia; it plays pivotal roles in RA pathogenesis by unfavorable behaviors such as producing inflammatory cytokines and chemokines, and hyperproliferation. MicroRNAs are evolutionarily conserved small non-coding RNAs (length is 18–25 nucleotides) that regulate gene expression at the post-transcriptional level. There is increasing interest in the involvement of microRNAs in autoimmune diseases including RA. Recent studies revealed the regulation of the function of FLS by microRNAs. Here, we review the known functional microRNAs in RA and summarize the potential uses of these small molecules in the treatment of RA.

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

Objective: Recently, Human T-cell leukemia virus type-1 proviral load (HTLV-1 PVL) has been evaluated as an important predictor of adult T-cell leukemia/lymphoma (ATL) in HTLV-1 carriers. We aimed ...

Aim We conducted this retrospective study to identify objective and comprehensive diagnostic criteria for early-stage rheumatoid arthritis (RA) that are based on ultrasound (US) and serologic findings. Method From August 2014 to May 2016, we recruited 216 consecutive patients at Hospital 1 and 223 consecutive patients at Hospital 2 who were suspected to have RA and underwent US of bilateral hands. In the US of bilateral hands from 22 sites, the findings obtained by grayscale and power Doppler (PD) assessments were each graded on a semi-quantitative scale from 0 to 3. We also examined the assessment of the novel outcome measures in rheumatology (OMERACT)-European League Against Rheumatism (EULAR) combined power Doppler ultrasound score (ie the cPD score) and the Global OMERACT-EULAR Synovitis Score. We used the US findings and the combination of US and serologic findings to evaluate the diagnostic performance of these modalities. Results Seventy patients (32.4%) at Hospital 1 and 59 patients (26.5%) at Hospital 2 were diagnosed as having RA. The best-balanced diagnostic performance at each hospital was achieved using a combination, such as (1) the presence of PD grade ≥2 articular synovitis or (2) the presence of PD grade ≥1 articular synovitis and serologic positivity, as well as by using (1) the presence of cPD grade = 3 or (2) a cPD grade ≥2 and serologic positivity. Conclusion The combination of a PD assessment or the cPD score with the measurement of autoantibodies of rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies can accurately identify patients with early-stage RA.

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.

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

To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the ‘treat-to-target’ strategy in clinical practice. We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients’ symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients’ clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient’s/evaluator’s global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. The value of the expected poor-prognosis factors may be diminished by intensive therapy within the ‘windows of opportunity’.

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.

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.

Objective We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). Methods We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. Results The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan–Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. Conclusions The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.

Objective To explore the variables associated with initial favorable power Doppler (PD) ultrasound (US) response induced by biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with rheumatoid arthritis (RA). Methods We have been prospectively investigating the course of active RA patients using US after the introduction of b/tsDMARDs in the Kyushu region of Japan since June 2013. One hundred fifty patients have completed the first 6 months of observation at present and have been evaluated. US was assessed in 22 joints of bilateral hands using gray-scale (GS) and PD images on a scale from 0 to 3. The sum of these scores was used as the indicator of US disease activity. We defined PD remission by total PD score=0 at 6 months and investigated the associated variables by multivariate logistic regression analysis. Results The total PD and GS scores and the clinical composite measures significantly improved at 6 months, whereas these reductions were less in bDMARDs switchers as compared with bDMARDs-naive patients. Multivariate logistic regression analysis showed that short disease duration (odds ratio 0.99, 95% confidence interval (CI) 0.99-1.00, p=0.031), the absence of any previous use of bDMARDs (odds ratio 0.27, 95% CI 0.10-0.68, p=0.0047) and low total PD scores (odds ratio 0.85, 95% CI 0.76-0.94, p=0.0003) at baseline were independent predictors of PD remission at 6 months. Conclusion The present prospective US cohort has for the first time shown the variables that are associated with initial PD response to b/tsDMARDs. This article is protected by copyright. All rights reserved.

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

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

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.

Background: Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs are important in rheumatoid arthritis (RA) treatment. The risk of hospitalized infection associated with bDMARDs/tsDMARDs in RA patients is unclear. Methods: We retrospectively analyzed the cases of the 275 RA patients with 449 treatment episodes who were administered a bDMARD/tsDMARD at Nagasaki University Hospital in July 2003-January 2015. We determined the incidence and risk factors of infection requiring hospitalization in the patients during a 3-year observation period. Results: Thirty-five (12.7%) of the patients experienced a hospitalized infection. The hospitalized infection risk did not differ significantly among several bDMARDs/tsDMARDs. A multivariate analysis revealed that the comorbidities of chronic lung disease (adjusted HR 5.342, 95% CI 2.409-12.42, p < 0.0001) and the initiation of bDMARDs/tsDMARDs before 2010 (adjusted HR 4.266, 95% CI 1.827-10.60, p = 0.0007) are significant independent risk factors for hospitalized infection. Compared to the before-2010 group, the group of patients whose treatment initiated in 2010 or later showed higher patient ages at the initiation of bDMARD/tsDMARD treatment and a higher rate of the use of prophylaxis with an antituberculosis agent, whereas the disease activities and number of the patients who received >5?mg of prednisolone were lower in the after-2010 group. Conclusions: This is the first report that the frequency of hospitalized infection significantly decreased when the patients were treated with a bDMARD or tsDMARD after 2010. Our results indicate that the updated announcement of diagnosis and treatment criteria might contribute to a reduced risk of hospitalized infection and a better understanding of the use of bDMARDs/tsDMARDs by rheumatologists., Journal of immunology research, 2018, 6259010; 2018

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.

A 67-year-old Japanese man was diagnosed with granulomatosis with polyangiitis based on the presence of right maxillary sinusitis, proteinase 3 antineutrophil cytoplasmic antibody positivity, and right scleritis. A conjunctival biopsy specimen showed neutrophil-predominant infiltration around the vessels without granuloma. Because there was a risk of blindness, pulsed methylprednisolone and intravenous cyclophosphamide pulse therapy (IVCY) were started. However, it was ineffective, and peripheral ulcerative keratitis newly emerged. We promptly switched the treatment from IVCY to rituximab, and ophthalmologists performed amniotic membrane transplantation, which avoided blindness. The close and effective working relationship between physicians and ophthalmologists improved our patient’s ocular prognosis., Internal Medicine57(12), pp.1783-1788; 2018

Objective We sought to identify the microRNA (miRNA) profile and potential biomarkers in FMF and to clarify their gene targets to elucidate the pathogenesis of FMF. Methods We performed an miRNA microarray using serum from FMF patients in attack and in remission. We then examined the expression of miRNAs in macrophages derived from THP-1 cells stimulated with toll-like receptor (TLR) ligands. Macrophages derived from THP-1 cells transfected with pre-miRNA were stimulated with lipopolysaccharides (LPSs) for the quantification of inflammatory cytokine production. To identify the target genes, we overexpressed their miRNA and performed a complementary DNA microarray. Transfection with reporter construct and the precursor miRNA was performed to confirm the suppression of target mRNA. Results We found that miR-204-3p was greatly decreased in the serum from FMF patients in attack. The expression of miR-204-3p was suppressed by LPS stimulation in the macrophages derived from THP-1 cells and the inhibition of miR-204-3p significantly induced the production of TLR4-related cytokines. The bioinformatic analysis showed that miR-204-3p is predicted to target genes implicated in the TLR pathway through the regulation of PI3Kγ signalling. The reporter assay revealed that miR-204-3p directly suppressed the luciferase activity of 3'-UTR of PIK3CG reporter construct. The inhibition of PI3Kγ resulted in decreased amounts of IL-6 and IL-12p40 in monocytes from FMF patients. Conclusion These data suggest that serum miR-204-3p has potential as a useful biomarker in FMF patients and that miR-204-3p serves as a suppressor of inflammatory cytokine production in FMF by targeting the PI3Kγ pathway.

A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) based on the detection of high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), vasculitis and granulomas in a lung biopsy specimen and crescentic glomerulonephritis in a kidney biopsy specimen. Soon after the initiation of intravenous methylprednisolone pulse therapy (mPSL pulse) and intravenous cyclophosphamide pulse therapy (IVCY), the patient experienced cough and hemoptysis. Based on emerging anemia and bilateral diffuse lung consolidation on computed tomography, we judged that diffuse alveolar hemorrhage (DAH) was complicated by GPA. The patient’s DAH improved following additional mPSL pulse and IVCY. Physicians should be aware of the possible occurrence of DAH, even when a patient’s symptoms improve after mPSL pulse and IVCY., Internal Medicine, 57(3), pp.417-421; 2018

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis and giant cell arteritis (GCA), also known as small-vessel vasculitis and large-vessel vasculitis, respectively, are sometimes difficult to distinguish by only the size and distribution of the vessels involved in daily clinical practice. We describe two cases of GCA with typical symptoms of GCA, i.e. a patient with jaw claudication complicated with microscopic polyangiitis (MPA), who had pleuritis, mononeuritis multiplex, interstitial pneumonia and scleritis. We treated the two cases as MPA and both patients achieved remission. When patients have atypical symptoms of GCA, not only GCA but also ANCA-associated vasculitis (AAV) should be investigated.

Objective: To identify potential biomarkers to distinguish adult-onset Still's disease (AOSD) from sepsis. Method: We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis. Results: Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%). Conclusion: Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines., Arthritis research & therapy, 22(1), art.no.108; 2020

Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.

Objectives: This study compared indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) and musculoskeletal ultrasound (MSUS), and explored the significance of the FOI findings based on the association between the FOI and MSUS findings and serum biomarkers in patients with rheumatoid arthritis (RA). The study also explored the association between the FOI findings and patients’ joint destruction at the joint-area level. Method: We enrolled 50 consecutive patients with active RA from among the patients hospitalized from May 2014 to March 2016 at Nagasaki University Hospital, Japan. FOI images were acquired with the Xiralite® fluorescence imaging system and compared with the patients’ clinical examination results and MSUS findings. On the same day, the patients’ clinical disease activity and levels of serum biomarkers (including vascular endothelial growth factor) were obtained. Results: Although the FOI detected synovitis with high sensitivity, the frequency of positive findings and the diagnostic performance with MSUS as the reference standard for FOI differed considerably among the phases of FOI as well as among the affected joint regions. The FOI scores were positively correlated with clinical disease activity, MSUS scores, and serum biomarkers. The severity of FOI-proven synovitis was associated with the presence of MSUS-proven bone erosion. Conclusion: FOI is effective for detecting joint inflammation in RA patients, with high accuracy. The severity of the FOI score was closely associated with the joint destruction at the joint-area level. However, the significance of positive FOI findings differed depending on not only the phase of FOI but also the affected joint regions.

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.