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Objectives: To update the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis (CPG for RA)., Methods: The recommendations were developed based on the evidence published until the end of June 2022 using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The steering committee, CPG panel, systematic review (SR) group, and SR support team were organised., Results: The treatment goal and drug treatment algorithm required no modifications; however, the footnotes of the drug treatment algorithm were modified. SR of 21 new or updated recommendations for subcutaneous methotrexate (n=1), biological disease-modifying antirheumatic drugs (n=1), rituximab (n=5), Janus kinase inhibitors (n=6), biosimilars (n=2), older patients (n=4), and pregnancy and lactation (n=2) was conducted. The recommendations for comorbidities and surgery and rehabilitation remained unchanged from the 2020 CPG for RA., Conclusion: The 2024 CPG for RA, which provide recommendations that reflect the current healthcare environment for RA in Japan, can be used effectively as a tool for shared decision-making between rheumatologists and patients in the treatment of RA., (© Japan College of Rheumatology 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated., Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly., Conclusion: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg)., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objective: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance., Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members., Results: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach., Conclusion: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines., Methods: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members., Results: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopaedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA., Conclusions: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objective: To determine whether patients with polymyalgia rheumatica (PMR) are more susceptible to glucocorticoid-induced adrenal insufficiency, one of the barriers to glucocorticoid tapering strategies, compared to patients with rheumatoid arthritis (RA)., Methods: This cross-sectional study included PMR and RA patients who underwent adrenocorticotropic hormone (ACTH) tests to assess adrenal function. The eligibility criteria were as follows: previous use of prednisolone (PSL) ≥ 5 mg/day, use of PSL for six consecutive months before ACTH test, and current use of PSL at 5 mg/day or less. The association between disease type (PMR vs. RA) and insufficient adrenal response was assessed using logistic regression models., Results: Twenty-six of 34 (76.5%) patients with PMR and 13 of 37 (35.1%) patients with RA had insufficient adrenal response. Compared to patients with RA, patients with PMR were more likely to have insufficient adrenal response, even after adjusting for age, sex, and PSL dose (adjusted odds ratio, 6.75; 95% confidence interval, 1.78-25.60)., Conclusion: Patients with PMR have a higher risk of glucocorticoid-induced adrenal insufficiency than patients with RA. Assessing the adrenal function in patients with PMR will contribute to establishing a more appropriate glucocorticoid reduction strategy., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to evaluate patients' opinions regarding their rheumatoid arthritis (RA) therapy and to reflect the patients' perspectives in the 2020 update of the Japan College of Rheumatology clinical practice guidelines., Methods: A self-administered questionnaire was mailed to 1600 members of the Japan Rheumatology Friendship Association, who were randomly selected by age and prefecture., Results: A total of 1156 patients returned the questionnaire (response rate, 72.3%; mean age, 63.0 ± 11.9 years). Those who reported having discussed their treatment goals with their doctors (450 respondents, 38.9%) were more likely to be satisfied with their current medical care (odds ratio, 7.13; 95% CI 4.72-10.8) compared with those who had not discussed their goals nor had them explained (287 respondents, 24.8%). The benefits exceeded the adverse effects for all pharmacotherapy (methotrexate, corticosteroids, conventional synthetic antirheumatic drugs, biological agents, Janus kinase inhibitor, and anti-RANKL antibodies). However, while 74.2% of the respondents using biological agents perceived that 'the favorable aspects outweighed the unfavorable aspects,' most of those taking anti-RANKL antibodies (69.2%) felt uncertain., Conclusions: The questionnaire successfully collected information regarding patients' perceptions regarding their therapy. Further implementation of treat-to-target is necessary in Japan to improve patient satisfaction., (© 2021 Japan College of Rheumatology.)

Objectives: To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA)., Methods: We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications., Results: After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25-2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications., Conclusion: Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries., (© 2021 Japan College of Rheumatology.)

Objectives: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults., Methods: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications., Results: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively., Conclusion: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults., (© 2021 Japan College of Rheumatology.)

Objectives: This study aimed to evaluate the impact of exercise therapy on patient-reported outcomes (PROs) in rheumatoid arthritis (RA) as part of the process of updating the 2020 Japanese guidelines for the management of RA according to the Grading of Recommendations, Assessment, Development, and Evaluation system., Methods: We searched PubMed, Japana Centra Revuo Medicina Web, and the Cochrane Library (from 2009 to 2018) to identify articles that evaluated PROs of exercise therapy and RA disease activity., Results: A total of 662 articles were identified, including nine RCTs, and meta-analyses were performed on six RCTs on systemic exercise therapy and three RCTs on upper extremity exercise therapy. Analyzed exercise therapies were diverse, differing in target population, intervention method, and duration. Significant improvements were observed in the Health Assessment Questionnaire Disability Index (mean difference -0.35, 95% confidence interval (CI): -0.60 to -0.10), pain (standardized mean difference -2.04, 95% CI: -3.77 to -0.32), and SF-36. For upper extremity exercise therapy, significant improvements in PROs (Disabilities of the Arm, Shoulder, and Hand Questionnaire, Michigan Hand Outcome Questionnaire) were observed., Conclusion: Exercise therapy in RA treatment improves patient subjective assessment of pain, physical function, and quality of life., (© 2021 Japan College of Rheumatology.)

Objective: This study aimed to evaluate satisfaction with total joint replacement (TJR) surgery among patients with rheumatoid arthritis (RA)., Methods: We mailed questionnaires to randomly selected members of the Japan Rheumatism Friendship Association, stratified by age and prefecture, throughout Japan. The questionnaire collected demographic and clinical characteristics as well as patients' satisfaction with TJR and their current therapy., Results: Of the 1156 patients who returned the questionnaire, 339 (29.3%) responded that they had had TJR of any type. The mean age was 66.6 years, and 94.4% were women. The mean time period from the hip and knee TJR was 14-15 years. Over half of the patients who had had TJR were satisfied with the results, especially those who had had hip (89.6%) and knee TJR (87.3%), who reported a high level of satisfaction. Multivariable linear regression analysis revealed that, in patients with knee TJR, satisfaction with current therapy was significantly related to whether they were satisfied with the results of the surgery., Conclusion: Most patients with RA who had undergone TJR were satisfied with the results even after a long period of time, and their level of satisfaction was associated with their satisfaction with current therapy., (© 2021 Japan College of Rheumatology.)

Objectives: To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA., Methods: PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system., Results: Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98-1.10) and 0.84 (0.61-1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69-1.26) and 2.15 (0.55-8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76-1.12) and 1.41 (0.32-6.15) in those who continued the reference bDMARDs., Conclusion: Biosimilars and reference bDMARDs were equally useful for the management of RA., (© 2021 Japan College of Rheumatology.)

Objectives: To assess the effectiveness and safety of interferon-free direct-acting antiviral (DAA) therapy for patients with concomitant hepatitis C virus (HCV) infection and rheumatic diseases (RDs), including rheumatoid arthritis (RA). Methods: This was a single-center observational case-series study conducted in Japan from 2014 to 2018. The primary endpoint was the sustained virological response (SVR) rate 24 weeks after the end of therapy (EoT24). We also evaluated hepatological and rheumatological outcomes and adverse events. Results: Of the 2314 patients with RDs, 18 received DAA therapy (RA = 11, other RDs = 7). The SVR rate for the initial DAA therapy was 89% (16/18). The remaining two achieved SVR with secondary DAA therapy. Along with HCV elimination, hepatological parameters improved significantly from baseline to EoT24. During the study period, no patients newly developed cirrhosis or HCC after HCV elimination. Several patients showed improvement in RDs activity. In RA patients, the simplified disease activity index decreased significantly from baseline to EoT24 (median [interquartile range]: 11.53 [5.14-14.89] vs. 4.06 [2.08-9.05], respectively). On-treatment adverse events were minimal, while two patients experienced tuberculosis reactivation after EoT. Conclusion: DAA therapy was effective and safe, providing hepatological and rheumatological benefits in HCV-infected patients with RDs. Immune reconstitution following HCV elimination should be noted.

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease. Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics. Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH. Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

Objective: To assess risk factors for cytomegalovirus (CMV) disease with CMV re-activation in patients with rheumatic disease. Methods: The clinical data of consecutive patients with rheumatic disease who experienced CMV re-activation were examined. We evaluated the difference in various baseline factors at the first detection of CMV pp65 antigenemia on the development of CMV disease using logistic regression models. The changes of laboratory data in the 4 weeks before CMV re-activation were also assessed. Results: We identified 80 patients (median age [interquartile range] = 65.0 years [51.5-74.0]) with CMV re-activation. Oral candidiasis, serum albumin ≤30 g/L, and CMV pp65-positive cell count >5.6/10 5 polymorphonuclear leukocyte cells were found to be associated with CMV disease (odds ratio [OR] [95% CI] = 9.99 [2.02-49.50], 11.4 [1.94-67.40] and 6.80 [1.63-28.30], respectively). Moreover, decreases in serum albumin level and blood lymphocyte count in the 4 weeks before CMV re-activation also predicted CMV disease (OR [95% CI] = 2.02 [1.07-3.8] and 1.96 [1.09-3.54], respectively). Conclusion: In CMV re-activation patients with rheumatic disease, the presence of oral candidiasis, high CMV pp65 positive cell count, and hypoalbuminemia are possible risk factors for CMV disease.

We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept.

We describe the first reported case of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by low-dose tacrolimus in a patient with autoimmune disease. A 41-year-old man with systemic lupus erythematosus (SLE) developed hyponatremia induced by SIADH after administration of tacrolimus (0.06 mg/kg per day). In this case, the hyponatremia promptly resolved upon withdrawal of tacrolimus. This case strongly suggests that SIADH is a potentially important complication of tacrolimus administration, irrespective of dosage, and should be borne in mind whenever the drug is used.

This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat.

Interleukin-17 is a proinflammatory cytokine. Recent animal studies have shown that IL-17 plays a role in the initiation and progression of arthritis. However, whether IL-17 has a prominent role in human rheumatoid arthritis (RA) or not remains unclear. Here we investigated the role of IL-17 in patients with RA. cDNA was prepared from knee joint synovial tissues of RA (n = 11) and osteoarthritic (OA, n = 10) patients and PBMC of RA (n = 52) and healthy subjects (n = 34). IL-17 gene expression level was measured by real-time PCR, and was compared with various clinical parameters. IL-17 gene expression in synovial tissues of RA was similar to that in OA. IL-17 gene expression level in PBMC of RA patients was significantly higher than in the control. The response (changes in DAS) to two-week treatment with anti-TNF-alpha blockers (infliximab or etanercept) did not correlate with changes in IL-17 gene expression levels. The IL-17/TNF-alpha gene expression ratio at baseline (before treatment) tended to be lower in responders to the treatment. Expression of IL-17 gene in PBMC may be associated with the inflammatory process of RA. IL-17/TNF-alpha expression ratio is a potentially suitable marker of response to anti-TNF-alpha therapy.

A 29-year-old male presenting nephrotic syndrome and facial skin erythema was admitted to our hospital in September of 2000. We diagnosed him as having systemic lupus erythematosus (SLE) accompanied by lupus nephritis (WHO class V). The disease activity had decreased after treatment with methylprednisolone (m-PSL) pulse therapy, which was followed by oral PSL. Thereafter, when tapering the dosage from 60 to 30 mg/day, the lupus nephritis flared up and he was re-hospitalized in February of 2001. After successful retreatment with m-PSL pulse therapy followed by the tapering of the dosage from 60 to 30 mg/day, we used mizoribine (MZR) as a combination therapy. The lupus nephritis flared up again after tapering down to 17.5 mg/day of PSL. Then, we changed the MZR dosage from 150 mg/day in three divided daily doses to 200 mg/day in two divided daily doses. This modification increased the peak blood concentration (Cmax) of MZR from 0.63 to 1.55 microg/ml. At present, we have been able to successfully taper the dosage to 7.5 mg/day of oral PSL and the patient has achieved a state of remission without any side effects. Monitoring of the serum concentration of MZR is thus considered to be important for achieving effective therapy of SLE, especially for steroid-resistant lupus nephritis. If the serum concentration of MZR does not reach an effective level, then the dosage of MZR should be adjusted appropriately in order to maintain an adequate serum concentration of MZR.

This article describes a patient with rheumatoid arthritis (RA) with crescentic glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48-year-old woman with a 4-year history of RA was admitted with fever and elevated C-reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and urinalysis revealed proteinuria and hematuria. Because she was also suffering from episcleritis, vasculitis was considered. A renal biopsy was performed, which revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated vasculitis. We considered treatment with high-dose oral prednisolone for vasculitis, but the patient refused this treatment. We started MTX at a dose of 8 mg/week for RA from the time of admission, and the patient responded immediately. Biochemical parameters, including C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had decreased to 46 EU. In clinical studies, few patients have been reported with RA complicated with ANCA-associated CrGN. This case differs from previous cases in the treatment given. No high-dose steroid with intensive immunosuppression or plasma exchange was required.

A 37-year-old man was admitted to our hospital because of fever, polyarthralgia, and subcutaneous tumors. There was swelling of the bilateral wrists and ankles, and subcutaneous tumors over the bilateral elbow joints. Despite his complaints of multiple symptoms, clinical investigations failed to reveal any abnormality. Although laboratory parameters improved rapidly after steroid therapy, the symptoms remained unchanged, and there was an enormous discrepancy between the laboratory data and his symptoms. A biopsy specimen from one of the subcutaneous tumors revealed foreign-body granuloma associated with a foreign body fragment. Because the nursing staff later discovered that the patient had been carrying out self-injection, a diagnosis of Munchausen syndrome was made. Munchausen syndrome should be included in the differential diagnosis of rheumatic diseases.

We describe a case of Takayasu's arteritis discovered during the early stage (pre-pulseless stage). Cervical ultrasonography and multiplanar reconstruction (MPR) images obtained by computed tomography (CT) showed thickening and stenosis of the walls of the common carotid arteries. However, magnetic resonance arteriography (MRA), volume rendering (VR) imaging CT, and maximum intensity projection (MIP) imaging CT could detect no obvious abnormality. We emphasize the importance of noninvasive vascular investigation with cervical ultrasonography and MPR imaging CT to support the diagnosis of early-stage Takayasu's arteritis.

Abstract The cell adhesion molecule β-catenin mediates the transduction of wnt signals to various downstream events such as gene expression, cell proliferation, and cell adhesion. In this study, the results of reverse transcriptase polymerase chain reaction (RT-PCR) amplification showed that wnt1 and β-catenin expression increased in response to E. faecalis, and that the increases in wnt1 and β-catenin activated transcription of cyclin D1. Immunohistochemistry also showed that stimulating wnt1 with E. faecalis cell fractions leads to the stabilization and accumulation of β-catenin in the synovial membrane. On the other hand, the results of RT-PCR showed overexpression of various inflammatory cytokines, including IL-1-β, TGF-β, TNF-α, and IL-6, in the synovial membrane of joints injected with E. faecalis cell fractions. These findings suggest that expression of cyclin D1 is strongly dependent on β-catenin/Tcf and has a direct effect on the proliferation of synoviocytes, such as IL-1-β and TGF-β, that leads to inhibition of Fas-antigen-mediated apoptosis of synovial cells.

Abstract A 56-year-old man presented with hyperproteinemia and renal dysfunction associated with antineutrophil cytoplasmic antibodies (ANCA). He had had a ventriculoperitoneal shunt tube made of silicone implanted 4 years earlier. In his renal biopsy, necrotizing crescentic glomerulonephritis was identified: tests for both myeloperoxidase ANCA and proteinase 3 ANCA were initially weakly positive. Antinuclear and other autoantibodies were also present. We diagnosed ANCA-associated vasculitis, probably induced by the silicone tube.

Abstract Vitiligo is a very common disease and is suspected to be autoimmune in its pathogenesis. Many autoimmune complications, such as Hashimoto's thyroiditis, are reportedly associated with vitiligo. The pathogenesis of ankylosing spondylitis (AS) is also suspected to be autoimmune, triggered by some infection. We report a 56-year-old man with concurrent vitiligo and AS, and suggest that both diseases could have a common autoimmune background.

Abstract Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH.

Abstract A 24-year-old woman suffered from blurred vision and periorbital edema with remittent fever. She was diagnosed as having systemic lupus erythematosus (SLE), complicated with myopia and retinopathy and severe chemosis. Antiphospholipid syndrome (APS), hemophagocytic syndrome, and liver involvement were also proven. We considered that APS might cause chemosis as a result of thrombosis-induced perfusion failure in the conjunctiva. In such cases, APS should be considered and anticoagulation therapy associated with steroid therapy should be initiated. In systemic lupus erythematosus (SLE), chemosis, severe hepatitis, and hemophagocytic syndrome (HPS) are rare complications. It is well known that many cases of SLE are complicated with antiphospholipid syndrome (APS), which causes arteriovenous thrombosis. We report a case of SLE with transient myopia and severe chemosis complicated with severe hepatitis and HPS. As this patient had antiphospholipid antibodies, these ocular complications were considered to be related to APS.

Abstract A 57-year-old man presented with palpitations, shortage of breath on exertion, and rapidly progressive scleroderma. On admission, a computed tomographic scan of his lung showed active interstitial pneumonia. We treated him with d-penicillamine and intravenous pulse methylprednisolone. After this treatment, severe abdominal pain, microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal involvement appeared. We diagnosed him as having systemic sclerosis (SSc) complicated by thrombotic thrombocytopenic purpura. At postmortem, thromboses of capillaries, arterioles, and small arteries were found in several organs. As well as the differential diagnosis of SSc with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and renal involvement, we diagnosed scleroderma renal crisis (SRC), normotensive renal crisis (NRC), and SSc complicated by TTP. Typical SRC and NRC were excluded because his blood pressure was in the normal range without elevation of plasma renin activity or azotemia over his clinical course. Although distinguishing TTP from renal crisis is difficult, an evaluation of ultra-large multimers of von Willebrand factor (UL-vWF) concentration may be helpful in these situations.