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The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10–30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements.

Objectives The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. Methods In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. Results Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29–9.74) for patients aged ≥ 75 years and 3.53 (1.31–9.53) for pulmonary complications. Four patients maintained remission for 6 months. Conclusions The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.

To evaluate effectiveness and safety of rituximab (RTX) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan.In this prospective observational study, all patients with MPA and GPA administered RTX were enrolled at each institution. During observation period of two years, data up to six months was analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome.Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by 6th month and 50 were in remission at 6th month. During therapy, 38 serious adverse events (SAE) were observed in 24 patients, 21 serious infections (SI) in 16 patients, and nine patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in SAE (22.6 vs. 54.5 %), SI (11.3 vs. 45.4 %), and death (1.9 vs. 36.4 %). The hazard ratio (95 % CI) for SI was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months.Effectiveness and safety of RTX for MPA and GPA for up to 6 months was demonstrated.

Objective: We aimed to identify associations between patterns of large-vessel lesions of large-vessel giant cell arteritis (LV-GCA) and treatment outcomes.Methods: We extracted data on 68 newly-diagnosed patients with LV-GCA from a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014. Patients with or without aortic lesions were identified based on findings from contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT. Patients without aortic lesions were subdivided into LV-GCA with or without subclavian lesions. Primary outcome evaluation was failure to achieve clinical remission by week 24 and/or relapse within 104 weeks. Results: Aortic lesions were detected in 49 (72.1%) of the 68 patients with LV-GCA (defined as group 2). Patients without aortic lesions were classified as having LV-GCA with subclavian lesions (group 1, n=9) or LV-GCA without subclavian lesions (group 3, n=10). The mean age and proportion of patients with cranial lesions and polymyalgia rheumatica in LV-GCA with aortic lesions (group 2) was lower than in the other two groups, but these differences were not statistically significant. In group 2, 36 of the 49 patients had lesions in both the aorta and aortic branches. Stenosis of aortic branches at baseline was more frequently observed in group 1 (55.6%) than groups 2 and 3 (18.4% and 30.0%, respectively). Atypical lesions in group 3 included pulmonary, hepatic or mesenteric lesions. Mean time to achievement of low-dose GC treatment was not statistically significant among 3 groups. Methotrexate was administered at baseline to 0 %, 24.5%, and 20% in groups 1, 2, and 3, respectively. None of these patients received biologic agents. The cumulative rate of poor treatment outcomes over two years was 11.1%, 55.3%, and 88.0% in groups 1, 2, and 3, respectively (by Kaplan-Meier analysis). The mean time to poor outcome was significantly different between the groups. Conclusions: The patterns of large-vessel lesions were associated with the poor treatment outcomes and appear to be a pertinent factor for determining treatment strategies for LV-GCA.

Objectives and methods Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disorder that causes vasculitis in small blood vessels throughout the body. Low-density granulocytes (LDGs) in autoimmune diseases, such as SLE and AAV, might play a critical role in the pathogenesis of these diseases. Here, we aimed to determine the characteristics of LDGs in patients with AAV. We assessed the number of whole white blood cells, neutrophil extracellular traps (NETs) productivity, proportion of cell surface markers (e.g. CD10), responses to immunosuppressants, and proteomics of LDGs in patients with AAV. Results We found more LDGs in peripheral blood mononuclear cells (PBMCs) of patients with AAV than PBMCs of healthy controls (HCs) and confirmed that these LDGs in AAV produced more NETs than normal density granulocytes (NDGs) in HCs. We identified CD10-positive LDGs with mature neutrophil features and CD10-negative LDGs with immature granulocyte properties; the proportion of the two LDG types decreased and increased, respectively, in the patients during treatment. Proteomic analysis revealed that the two LDG groups shared protein expression that differed from those of NDGs. Conclusion We identified distinct CD10-positive and CD10-negative LDGs in patients with AAV. The roles of these LDGs in AAV pathology will require further investigation.

ObjectiveFollowing induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab.MethodsRITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse).ResultsRituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, pConclusionsFollowing induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse.Trial registration numberNCT01697267; ClinicalTrials.gov identifier

BackgroundTo evaluate long-term efficacy of infliximab (IFX) in refractory uveoretinitis associated with Behçet’s disease (BD) depending on uveoretinitis duration.MethodsRecords of 16 patients with BD (32 eyes) followed for >5 years after starting IFX, were retrospectively reviewed. Long-term efficacy was compared between patients with short duration (≤18 months, n=7) versus long duration (>18 months, n=9) of their uveoretinitis prior to starting IFX.ResultsThe median follow-up after starting IFX was 132 months (76–146 months). Mean frequency of attacks and the 1-year Behçet’s Disease Ocular Attack Score 24 decreased significantly over 10 years. Overall, the percentage of eyes with a best-corrected visual acuity (BCVA) ≥1.0 increased from 47% at baseline to 59% at 5 years; the percentage of eyes with a BCVA ≤0.1 was 19% at both baseline and 5 years. The frequency of ocular attacks decreased similarly in both short duration and long duration groups; however, the percentage of eyes with a BCVA ≥1.0 at 5 years was 100% in the short duration group versus 28% in the long duration group. IFX was discontinued in four patients with an excellent response to IFX therapy; all were young male patients in the short duration group with good BCVA bilaterally, and none had inflammatory recurrences over a median follow-up of 56 months off IFX.ConclusionInitiation of IFX therapy in patients with BD within 18 months of their uveoretinitis onset was more effective in maintaining good BCVA than after 18 months.

Background and aims Small intestinal lesions in patients with Behcet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. Methods This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. Results Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 μg/g) and FL (cutoff value = 17 μg/g) were biomarkers for small intestinal lesions in patients with BD. Conclusion The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic disease that causes vasculitis in various organs. Although the cause of the onset is unknown, infection has been reported to be a causative factor. The subsequent cytokine storm triggered by the immune response against SARS-CoV-2 infection has been reported to lead to symptoms being more severe. We herein report our experience with the onset of AAV following COVID-19 infection. We also report the course of anti-SARS-CoV-2 serum antibody titers following induction therapy, which suggests that vaccination and education concerning standard precautions are necessary in patients who require immunosuppressive therapy, even after COVID-19 infection.

ObjectiveTo evaluate whether the distribution of large-vessel lesions (LVLs) in giant cell arteritis (GCA) is associated with poor treatment outcomes.MethodsIn a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014, 68 newly-diagnosed patients with LVLs were identified by imaging. Non-achievement of clinical remission by week 24 and/or relapse within 104 weeks were primarily evaluated. Factors influencing the poor treatment outcome were analyzed using Cox proportional hazard modeling. Cumulative rates and median time to the first event were analyzed by the Kaplan-Meier method and log-rank testing.ResultsAortic lesions were detected in 72.1% of the 68 GCA patients with LVLs (defined as group 2). Patients without aortic lesions were classified as having large-vessel GCA with subclavian lesions (group 1) or atypical large-vessel GCA without subclavian lesions (group 3). The mean age and proportions of PMR in group 3 were higher than those in the other two groups. Cranial lesions were observed in 66.7%, 55.1%, and 80.0% of patients in groups 1, 2 and 3, respectively. In group 2, 73.5% had lesions in both the aorta and aortic branches. Group 1 had axillary lesions in 33.3%, and carotid lesions in 44.4%. Atypical LVLs in group 3 included pulmonary, hepatic or mesenteric lesions in addition to carotid lesions. Baseline doses of GCs were not different across the groups. Mean time to achievement of low-dose GC treatment (prednisolone ≤5 mg/day) was also not significantly different between the groups. The cumulative rate of poor treatment outcome over the two years was 11.1%, 55.3% and 88.0% in the groups 1, 2 and 3, respectively; mean time to the events was significantly different among the groups. Multivariable analysis showed that the risk of poor treatment outcome was significantly higher in the group 3.ConclusionsThe distribution of LVLs was associated with treatment outcomes in large-vessel GCA. In addition to subclavian arteries, lesions in aorta and aortic branches other than subclavian arteries should be evaluated by imaging for large-vessel GCA. The pattern of LVLs determined by imaging should be considered when determining treatment strategies for GCA.

Infection control at nursing homes is a top priority to address the COVID-19 pandemic because people who are the most vulnerable to the pathogen live in close contact. Currently, control measures specifically for nursing homes often ignore under-resourced condition of the facilities. To make guidelines assuming realistic conditions, an expert meeting with 16 members established the key challenges in nursing homes, the basics of infection control, and the major transmission routes. A list of existing guidance was compiled and each item in the list was peer-reviewed by eight experts considering three aspects: significance, scientific validity, and feasibility. Factors related to the nursing home environment, the nature of SARS-CoV-2 transmission, and patient characteristics were identified as the causes of difficulties in infection control at nursing homes. To develop realistic prevention measures in under-resourced condition such as nursing homes, we may need to accept there are no perfect control measures that can achieve zero risk. Instead, the guidelines are based on the concept of deep defense, and practical checklists with 75 items were established. The evaluation of nursing homes by independent organizations using the checklists would be helpful to achieve sustainable infection control.

ObjectivesTo delineate characteristics of non-radiographic axial spondyloarthritis (nr-axSpA) in Asia versus non-Asian regions, and compare radiographic axSpA (r-axSpA) with nr-axSpA within Asia.MethodsData were collected from the Assessment of SpondyloArthritis international Society-COMOrbidities in SPondyloArthritis database. Categorising patients by region, we compared clinical characteristics between nr-axSpA from Asia vs elsewhere (Europe, the Americas and Africa). Within Asians, we additionally compared patient characteristics of those with nr-axSpA versus r-axSpA.ResultsAmong 3984 SpA cases, 1094 were from Asian countries. Of 780 axSpA patients in Asia, 112 (14.4%) had nr-axSpA, less than in non-Asian countries (486/1997, 24.3%). Nr-axSpA patients in Asia were predominantly male (75.9% vs 47.1%), younger at onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years), and experienced less diagnostic delay (1.9 vs 2.9 years) compared with nr-axSpA in non-Asian countries. Nr-axSpA in Asia exhibited higher human leucocyte antigens-B27 prevalence (90.6% vs 61.9%), fewer peripheral SpA features (53.6% vs 66.3%) and similar extra-articular and comorbid disease rates compared with those with nr-axSpA in non-Asian countries. Disease activity, functional impairment and MRI sacroiliitis were less in nr-axSpA in Asia, with higher rates of non-steroidal anti-inflammatory drug response and less methotrexate and biological disease-modifying antirheumatic drugs use. Within Asia, r-axSpA showed higher disease activity and structural damage compared with nr-axSpA, with no differences in other features.ConclusionAmong axSpA, lower frequency of nr-axSpA was observed in Asia. Our results offer an opportunity to better understand clinical characteristics and optimise diagnostic strategies, such as ensuring access and availability of MRI resources for accurate diagnosis of nr-axSpA in Asia.

Objectives In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey. Methods Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed. Results We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively. Conclusions MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey.

Non-small cell lung carcinoma unusually causes clinically relevant metastases in the kidney while they are usually found only in autopsy. Acute kidney injury (AKI) due to direct metastatic invasion of a solid tumor is also very rare whereas it usually happens with hematologic malignancy, including lymphoma. We report a case with these two rarities. A 54-year-old man who had a 6.7 × 6.0 cm-sized tumor in the left upper lobe of the lung in computed tomography was diagnosed as squamous cell lung carcinoma with bronchoscopy with biopsy. His renal function was normal and no proteinuria or hematuria was recognized. He underwent left upper lobectomy and the pathologic examination revealed pT4N1M0 stage IIIA disease. Four months after the surgery, a single brain metastasis in the right frontal lobe found in brain magnetic resonance imaging was treated with Gamma Knife radiosurgery. He presented with macroscopic hematuria and AKI (the serum creatinine level was 1.35 mg/dL) nine months after surgery. The cause was enormous bilateral renal metastases, maximally 8 cm-sized lesions with poor enhancement, which were found in enlarged bilateral kidneys in enhanced CT. Intrapulmonary metastatic lesions were also newly detected. Chemotherapy with pembrolizumab, an antibody against anti-programmed cell death protein 1, had little effect and his renal function continued to decline rapidly, resulting in end-stage renal disease and maintenance hemodialysis. Chemotherapy with carboplatin and paclitaxel was additionally performed. However, two months after hemodialysis induction, the patient died with pneumonia and acute respiratory distress syndrome.

ObjectivesEvaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.MethodsPatients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.Results188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.ConclusionsThis large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Tubulointerstitial nephritis and renal tubular acidosis are well-known renal involvements with primary Sjogren’s syndrome. However, several types of glomerulonephritis such as membranoproliferative glomerulonephritis and membranous nephropathy are also known to develop in patients with this syndrome. We here report a case of membranous nephropathy that developed 8 years after a diagnosis of primary Sjogren’s syndrome in a female patient. Interestingly, the deposition was not identified by routine immunofluorescence using snap frozen tissue, but was revealed by immunofluorescence on formalin-fixed paraffin-embedded sections treated with proteinase K. We further performed immunofluorescence analysis on the treated paraffin-embedded sections with the identified antigen but found that the deposited IgG was not monoclonal and that serum amyloid P, a sensitive marker for membranous-like glomerulopathy with masked IgG κ deposits, was not evident in the glomeruli. To the best of our knowledge, this report depicted the first case of masked polyclonal IgG deposits and further analysis is needed to clarify the underlying mechanisms of IgG masking and possible association with autoantibodies.

Background The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). Case presentation A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient’s laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient’s renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. Conclusion On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Patient: Female, 74 Final Diagnosis: Tenosynovitis Symptoms: Arthralgia • pain Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Rheumatoid arthritis tenosynovitis is difficult to discriminate from non-tuberculous tenosynovitis on the basis of radiological and pathological findings. Case Report: A 74-year-old woman with a 4-year history of rheumatoid arthritis was referred to our hospital to undergo treatment for uncontrollable tenderness and swelling in her right third metacarpophalangeal joint, right wrist, and left knee joint. In the previous year, she underwent surgery at a local hospital for the swelling in her right metacarpophalangeal joint, the information of which was not known precisely, but the swelling subsided in due course after an operation. We treated the patient with infliximab (monthly intravenous infusions of 150 mg), but 2 months later, she complained of exacerbation of the swelling in her right third metacarpophalangeal joint and right wrist, and fluid discharge that contained Mycobacterium intracellulare. After synovectomy and aggressive debridement in the palmar side of the right wrist, she was diagnosed as having granulomatous tenosynovitis caused by the M. intracellulare infection and abundant rice body formation in the right carpal tunnel area. We considered the rice bodies inside and outside the bursa, along with a history of tenosynovitis exacerbation after initiation of infliximab therapy (tumor necrosis factor alpha inhibitor [TNFi]), to be related to the M. intracellular infection. Conclusions: Tenosynovitis caused by atypical mycobacteria is uncommon and usually affects the hand or wrist. Therefore, for early diagnosis, mycobacterial infection should be considered in cases of indolent chronic granulomatous tenosynovitis, especially in RA cases that recur after TNFi therapy is started.

Psoriatic arthritis (PsA) is associated with decreased quality of life. As delayed diagnosis may lead to progressive joint destruction and long-term disability, the key clinical features of PsA should be recognizable to a wide range of clinicians to facilitate early diagnosis. In addition to assessment and identification of skin and nail lesions, which occur in up to 85% of those with musculoskeletal manifestations, clinicians should be aware of both the peripheral and axial manifestations of musculoskeletal disease reviewed here. Peripheral joint diseases include polyarticular, oligoarticular, distal, and arthritis mutilans subtypes, and cognizance of these patterns of disease, as well as periarticular manifestations, including dactylitis and enthesitis, is useful for swift diagnosis of PsA. Axial psoriatic arthritis (axial PsA), also known as the spondylitis subtype, may be limited to the spine and sacroiliac joints, but may also affect peripheral structures. Meticulous history-taking and physical examination and familiarity with appropriate imaging studies are often necessary to distinguish axial-PsA from other differential diagnoses. Swift diagnosis and treatment are necessary to both control PsA disease and mitigate the risks of the many associate comorbidities that may accompany it.

Background:Clinical characteristics of nonradiographic axial spondyloarthritis (nr-ax-SpA) are highly variable across patients, and may potentially vary across patient populations, particularly due to differing distributions of human leukocyte antigens (HLA) and other genetic factors. The majority of nr-ax-SpA studies have been conducted in Europe, the United States, and small studies are reported from Asia [1].Objectives:To delineate clinical characteristics of patients with nr-ax-SpA in Asian countries in comparison to other areas of the world.Methods:Utilizing the ASAS-COMOSPA data, an international cross-sectional observational study of SpA patients, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Asia (China, Japan, Singapore, South Korea, and Taiwan), and non-Asian countries (Europe, Americas, and Africa); patient characteristics, including diagnosis and treatment, were compared.Results:Among 3984 SpA patients included in the study, 1094 were from centers in Asian countries, and 2890 from other regions. 112/780 (14.4%) of axial SpA patients in Asian countries were nr-ax-SpA, substantially less than in other countries (486/1997, 24.3%). Nr-ax-SpA patients in Asian countries compared to nr-ax-SpA in other countries were more likely male (75.9 vs 47.1%), have onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years) at younger age, and experience less diagnostic delay (1.88 vs 2.92 years) (Table 1). Nr-ax-SpA patients in Asian countries have higher prevalence of positive HLA-B27 (90.6% vs 61.9%) and fewer peripheral signs such as arthritis, enthesitis, or dactylitis (53.6% vs 66.3%) but have similar rate of extra-articular manifestations (psoriasis, IBD, or uveitis) and co-morbidities. Disease activity, functional impairment, and inflammation on MRI were less in nr-ax-SpA patients in Asian countries. NSAIDs response was higher and use of methotrexate and b-DMARDs were lower among nr-ax-SpA in Asian countries.Conclusion:Among axial SpA patients, substantially lower frequency of nr-ax-SpA was observed in Asian countries compared to other regions of the world. Nr-ax-SpA patients in Asian countries were predominantly male, and had younger disease onset with higher HLA-B27 positivity rate and less peripheral signs, and better response to NSAIDs. These results offer an opportunity to improve both early diagnosis and treatment of nr-ax-SpA patients in Asian countries.Table 1.Characteristics of nonradiographic axial SpA in Asia versus non-Asian regionsVariablesAsianon-Asian regionsp valueN112486Age at disease diagnosis, yrs27.2 [21.1, 39.6]34.5 [27.7, 41.7]Diagnostic delay, yrs1.88 [0.27, 5.56]2.92 [0.59, 9.58]0.011Male (%)85 (75.9)229 (47.1)Sacroiliitis on MRI among tested (%)49 (67.1)341 (82.2)0.005HLA B27 positivity among measured (%)96 (90.6)273 (61.9)Inflammatory Back Pain (%)107 (95.5)478 (98.4)0.076Arthritis, enthesitis, or dactylitis (%)60 (53.6)322 (66.3)0.016Psoriasis (%)12 (10.7)82 (16.9)0.142Uveitis (%)20 (17.9)81 (16.7)0.870Inflammatory bowel disease (%)5 (4.5)27 (5.6)0.817Elevated CRP (%)37 (33.0)213 (43.8)0.048Physician global assessment (0-10)2.0 [1.0, 5.0]2.0 [1.0, 4.0]0.741Patient global assessment (0-10)3.0 [1.0, 6.0]4.0 [2.0, 6.0]0.012ASDAS-CRP1.40 [0.95, 2.08]1.97 [1.21, 2.78]BASFI0.8 [0.05, 2.65]2.9 [0.8, 5.6]Good response to NSAIDs (%)80 (71.4)272 (56.0)0.004Methotrexate use (%)18 (16.1)134 (27.6)0.016Biological DMARDs use (%)27 (24.1)191 (39.3)0.004References:[1]López-Medina C, Ramiro S, van der Heijde D, et al. Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis. RMD Open. 2019 Nov 21;5(2): e001108.Acknowledgements:This study was conducted under the umbrella of the International Society for Spondyloarthritis Assessment (ASAS) and COMOSPA study was supported by unrestricted grants from Pfizer, AbbVie and UCB.Disclosure of Interests:Keisuke Ono: None declared, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Sho Fukui: None declared, Satoshi Kawaai: None declared, Gautam A. Deshpande: None declared, Kazuki Yoshida Consultant of: OM1, Inc., Grant/research support from: Corrona, LLC, Naomi Ichikawa: None declared, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB, Taku Kawasaki: None declared, Kazuo Matsui: None declared, Mitsuhiro Morita: None declared, Kurisu Tada: None declared, Naoho Takizawa: None declared, Naoto Tamura: None declared, Atsuo Taniguchi: None declared, Yoshinori Taniguchi: None declared, Shigeyoshi Tsuji: None declared, Shigeto Kobayashi: None declared, Masato Okada: None declared, Clementina López-Medina: None declared, Anna Moltó Consultant of: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Grant/research support from: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Imaging Rheumatology bv. (Director), Maxime Dougados: None declared, Yoshinori Komagata: None declared, Tetsuya Tomita: None declared, Shinya Kaname: None declared.

Background:Giant cell arteritis (GCA) is characterized by cranial symptoms and large-vessel lesions (LVL) in the aorta or its branches. We retrospectively analyzed the Japanese patients newly diagnosed as GCA between 2007 and 2014, and subsequently treated with glucocorticoid (GC). The imaging studies revealed that LVLs were observed in approximately half of the GCA patients, and the LVLs were significantly associated with the increased probability of poor treatment outcomes (1).Objectives:The objective of this study is to evaluate whether the distribution of LVLs of GCA was associated with poor treatment response.Methods:In a retrospective, multi-centric, nationwide registry of GCA patients treated with GCs between 2007 and 2014, 68 newly-diagnosed GCA with LVLs by imaging were detected. All investigators were members of Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS). Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 104 weeks) were primarily evaluated. Cumulative rates and median time to the first event were analyzed by the Kaplan-Meier method and the log-rank test. Associated factors with the outcomes were analyzed by using the Cox proportional hazard model.Results:The mean age was 70.5 years, and 70.6% were women. Twenty-seven (39.7%) of the 68 patients were diagnosed as having GCA by both positive temporal artery biopsy and positive imaging, and 41 (60.3%) by positive imaging. Aortic lesions were detected in 72.1% (group 2, n=49) of the 68 GCA patients with LVLs. Patients without aortic lesions were categorized into two phenotypes: large-vessel GCA with subclavian lesions (group 1, n=9) and atypical large-vessel GCA without subclavian lesions (group 3, n=10). Cranial lesions were observed in 66.7%, 55.1%, and 80.0% in the group 1, 2, and 3, respectively. The initial mean dose (SD) of prednisolone was 0.74 (0.26) mg/kg/day, and 20.6 % received methotrexate for remission induction therapy. Baseline dose of GCs and mean time to achievement of low-dose GCs (prednisolone ≤ 5 mg/day) was not significantly different among the three groups.Overall, 35 (51.5%) of the 68 patients had the event of poor treatment outcomes. Eleven patients were not able to achieve clinical remission by week 24. Relapse after achievement of clinical remission was reported in total of 24 patients; 9 between week 0 and 24, 12 between week 24 and 52, 3 between week 52 and 104. The cumulative rate of events of poor treatment outcomes over the two years was 11.1% in patients with group 1, 55.3% in those with group 2, and 88.0% in those with group 3. Mean time to events was significantly different among the three groups. Multivariable analysis showed the risk of poor treatment outcomes was likely to decrease in the group 1 (hazard ratio 0.14 [95% CI 0.02-1.03], p=0.054), while it increased in the group 3 (hazard ratio 2.22 [95% CI 1.06-4.68], p=0.035).Conclusion:The distribution of LVLs were associated with poorer treatment outcomes. A half of the patients with aortic lesions had poor treatment outcomes while subclavian arteritis without aortic lesions had better clinical outcomes. Atypical large vessel-GCA without the aortic and subclavian artery involvement was the worst prognostic phenotype of LV-GCA. Extent of LVLs by imaging should be considered when determining the treatment strategy for GCA.References:[1]Sugihara T, et al. Arthritis Res Ther. 2020;22(1):72Acknowledgements:The authors would like to acknowledge Mitsuaki Isobe (Sakakibara Heart Institute), Yoshihiro Arimura (Kichijoji Asahi Hospital), and all the investigators in the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS). In addition to the authors, the following investigators and institutions participated in this study: Department of Internal Medicine, Juntendo University Koshigaya Hospital (Shigeto Kobayashi); Niigata Rheumatic Center (Satoshi Ito); Niigata Prefectural Shibata Hospital (Noriyuki Homma).Disclosure of Interests:takahiko sugihara Speakers bureau: TS has received honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd., Grant/research support from: TS has received research grants from AsahiKASEI Co., Ltd., Daiichi Sankyo., and Ono Pharmaceutical., Haruhito A. Uchida Grant/research support from: HAU belongs to the Department of Chronic KidneyDisease and Cardiovascular Disease which is endowed by Chugai Pharmaceutical, MSD, Boehringer Ingelheim, and Kawanishi Holdings., Hajime Yoshifuji Speakers bureau: HY has received lecture fees from Chugai Pharmaceutical Co., Ltd. and Nihon Medi-Physics Co., Ltd., Yasuhiro Maejima Speakers bureau: YM have received honoraria from Chugai Pharmaceutical Co., Ltd.., Taio Naniwa Speakers bureau: TN has received lecture fees from Chugai Pharmaceutical Co., Ltd.., Grant/research support from: TN has received research grants from Chugai Pharmaceutical Co., Ltd.., Yasuhiro Katsumata Speakers bureau: YK has received honoraria from Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., Sanofi K.K., Pfizer Japan Inc., and Asahi Kasei Pharma Corp., Takahiro Okazaki Grant/research support from: TO has received research grants from Chugai Pharmaceutical Co., Ltd., Eisai Pharmaceutical., and Actelion, Jun Ishizaki: None declared, Yohko Murakawa Speakers bureau: YM has received honoraria from Abbvie, Astellas, Ayumi Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Kissei Pharmaceutical, Nippon Kayaku, Pfizer Pharmaceutical, Takeda Pharmaceutical, UCB Pharmaceutical, Grant/research support from: YM has received research grant support from Asahi Kasei Pharma, AbbVie Japan, Chugai Pharmaceutical, Daiichi Sankyo, Eisai Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Gilead Sciences Inc, Janssen Pharmaceutical, and Teijin Pharma., Noriyoshi Ogawa: None declared, Hiroaki Dobashi: None declared, Tetsuya Horita: None declared, Yoshiya Tanaka Speakers bureau: YT has received consulting fees, speaking fees, and/or honoraria from Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, UCB, Grant/research support from: YT has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa- Kirin, Eisai, Ono., Shunsuke Furuta: None declared, Tsutomu Takeuchi Speakers bureau: TT has served on speakers’ fees for AbbVie, Bristol-Myers Squibb, Chugai, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Eisai, Sanofi, Teijin, Takeda, and Novartis., Consultant of: TT has received consulting fees from Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, AbbVie, Nippon Kayaku, Janssen, Astellas, Taiho, Chugai, Taisho Toyama, GlaxoSmithKline, and UCB., Grant/research support from: TT has received research grants from Astellas, Chugai, Daiichi Sankyo, Takeda, AbbVie, Asahi Kasei, Mitsubishi Tanabe, Pfizer, Eisai, AYUMI, Nippon Kayaku, and Novartis., Yoshinori Komagata Speakers bureau: YK has received speakers’ fees from Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Daiichi Sankyo, AbbVie, Nippon Shinyaku, Towa., Consultant of: YK has received consulting fees from Chugai, Kyowa Hakko Kirin, Asahi Kasei, UCB, Yoshikazu Nakaoka Speakers bureau: YN has received lecture fees from Astellas, Takeda, Daiichi Sankyo, Actelion, and Japan Blood Products Organization (JB)., Consultant of: YN has received consulting fees and/or lecture fees from AbbVie and Chugai, Grant/research support from: YN has received research grants from Chugai and Bayer Yakuhin, Ltd, masayoshi harigai Speakers bureau: MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: MH is a consultant for AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: MH has received research grants from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.

Reactive arthritis (ReA) is typically preceded by sexually transmitted disease or gastrointestinal infection. An association has also been reported with bacterial and viral respiratory infections. Herein, we report the first case of ReA after the he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This male patient is in his 50s who was admitted with COVID-19 pneumonia. On the second day of admission, SARS-CoV-2 PCR was positive from nasopharyngeal swab specimen. Despite starting standard dose of favipiravir, his respiratory condition deteriorated during hospitalisation. On the fourth hospital day, he developed acute respiratory distress syndrome and was intubated. On day 11, he was successfully extubated, subsequently completing a 14-day course of favipiravir. On day 21, 1 day after starting physical therapy, he developed acute bilateral arthritis in his ankles, with mild enthesitis in his right Achilles tendon, without rash, conjunctivitis, or preceding diarrhoea or urethritis. Arthrocentesis of his left ankle revealed mild inflammatory fluid without monosodium urate or calcium pyrophosphate crystals. Culture of synovial fluid was negative. Plain X-rays of his ankles and feet showed no erosive changes or enthesophytes. Tests for syphilis, HIV, anti-streptolysin O (ASO), Mycoplasma, Chlamydia pneumoniae, antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide antibody and Human Leukocyte Antigen-B27 (HLA-B27) were negative. Gonococcal and Chlamydia trachomatis urine PCR were also negative. He was diagnosed with ReA. Nonsteroidal Anti-Inflammatory Drug (NSAID)s and intra-articular corticosteroid injection resulted in moderate improvement.

Background Patients with Sjögren’s syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy. Methods The pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability. A prospective clinical trial was undertaken to assess the efficacy and safety of the LPA solution as a symptomatic treatment for dry mouth in SS. Patients (n = 24) with clinically significant xerostomia were enrolled after providing written informed consent. Whole-mouth salivary flow rate was measured twice; immediately before and 60 min after LPA application. Symptoms were assessed by questionnaire with visual analog scales or checkboxes before the first application (baseline), and then once daily for 7 days. Results The pilocarpine content 3, 7, 14, and 28 days after preparation showed no marked change, confirming its stability. Salivary flow was significantly increased from 0.076 ± 0.092 g/30 s to 0.122 ± 0.140 g/30 s 60 min after LPA administration (P