Establishing clinical remission criteria for giant cell arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis.

OBJECTIVE: To develop a proposal for giant cell arteritis remission criteria in order to implement a treat-to-target algorithm. METHODS: A task force consisting of 10 rheumatologists, 3 cardiologists, 1 nephrologist, and 1 cardiac surgeon was established in the Large-vessel Vasculitis Group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis to conduct a Delphi survey of remission criteria for giant cell arteritis. The survey was circulated among the members over four reiterations with four face-to-face meetings. Items with a mean score of ≥4 were extracted as items for defining remission criteria. RESULTS: An initial literature review yielded a total of 117 candidate items for disease activity domains and treatment/comorbidity domains of remission criteria, of which 35 were extracted as disease activity domains (systematic symptoms, signs and symptoms of cranial and large-vessel area, inflammatory markers, and imaging findings). For the treatment/comorbidity domain, ≤5 mg/day of prednisolone 1 year after starting glucocorticoids was extracted. The definition of achievement of remission was the disappearance of active disease in the disease activity domain, normalization of inflammatory markers, and ≤5 mg/day of prednisolone. CONCLUSION: We developed proposals for remission criteria to guide the implementation of a treat-to-target algorithm for giant cell arteritis.

Association between glucocorticoid discontinuation and incidence of infection in older adults with rheumatoid arthritis: A retrospective cohort study.

AIM: Old age and glucocorticoid (GC) use increase the susceptibility to infection in patients with rheumatoid arthritis (RA). Accordingly, we investigated whether GC discontinuation reduces the incidence of infection in older adults with RA and analyzed factors associated with GC discontinuation. METHODS: Medical records of patients with RA aged ≥60 years were retrieved, and the association between GC use and the incidence of infection was investigated. The participants were divided into three groups: GC-continued, GC-discontinued, and non-GC; the incidence of infection was statistically analyzed. Furthermore, patient treatments and comorbidities were examined. RESULTS: Among 389 patients with RA included in the study (n = 122, n = 126, and n = 141 in the GC-discontinued, GC-continued, and non-GC groups, respectively), 65 (16.7%) patients developed infection, and the incidence of infection was significantly higher in the GC-continued group than in the GC-discontinued (p = .021) and non-GC (p = .0003) groups; there was no significant difference between the non-GC and GC-discontinued groups (p = .659). The GC-discontinued group was more likely to require biologic use throughout the disease course than the other two groups. Comorbidities, especially malignancies (p = .004), were more common in the GC-continued group than in the GC-discontinued group (p = .007). CONCLUSION: In patients with RA aged ≥60 years receiving GCs, GC discontinuation reduced the incidence of infection. Therefore, a further analysis of factors that help reduce GC use is necessary.

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

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

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

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.

Long-term survival, causes of death, and prognostic factors for mortality in patients with microscopic polyangiitis and those with anti-neutrophil cytoplasmic antibody-positive interstitial lung disease: A single-center retrospective study.

AIM: To elucidate the clinical features, long-term survival, and prognostic factors for mortality among patients with microscopic polyangiitis (MPA), including those with anti-neutrophil cytoplasmic antibody-positive interstitial lung disease (ILD) (ANCA-ILD), which could be a subset of its variant phenotype. METHODS: We retrospectively included 76 consecutive patients between 2006 and 2014, diagnosed with MPA according to the European Medicines Agency algorithm using the Chapel Hill Consensus Conference definitions or ANCA-ILD. ILD was classified as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia pattern using chest computed tomography. RESULTS: The mean (standard deviation) age of the patients (female, 68%) was 69 (12) years. The median (interquartile range) follow-up period was 68 (33-95) months. Comorbid ILD and glomerulonephritis were observed in 44 (58%) (68% UIP) and 54 (71%) patients, respectively. Comorbid ILD was associated with low survival (P = .0563). There were 17 (39%) and 5 (16%) deaths in the ILD and non-ILD groups, respectively (P = .0404). In the ILD group, 6 and 5 of the deaths were attributed to infection and ILD progression, respectively. In the non-ILD group, 1 and 2 patients expired from subsequently developed ILD and aspiration pneumonia, respectively. Age ≥ 70 years (hazard ratio = 2.78; 95% confidential interval 1.15-6.70) and UIP (3.95; 1.60-9.77) were independent risk factors for mortality. CONCLUSION: Age ≥ 70 years and ILD with a UIP pattern were associated with high mortality, owing to susceptibility to infection and ILD progression. A more effective and less toxic treatment is required for progressive ILD.

Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines.

BACKGROUND: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. METHODS: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. RESULTS: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. CONCLUSIONS: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.

Establishing clinical remission criteria and the framework of a treat-to-target algorithm for Takayasu arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour and Welfare for intractable vasculitis.

OBJECTIVES: To develop a proposal for remission criteria and a framework for a treat-to-target (T2T) algorithm for Takayasu arteritis (TAK). METHODS: A study group of the large-vessel vasculitis group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis consists of 10 rheumatologists, 5 cardiologists, 1 nephrologist, 1 vascular surgeon, 1 cardiac surgeon, and 2 paediatric rheumatologists. A Delphi survey of remission criteria items was circulated among the study group over four reiterations. To develop the T2T algorithm, the study group conducted four face-to-face meetings and two rounds of Delphi together with three patients. RESULTS: Initial literature review resulted in a list of 117 candidate items for remission criteria, of which 56 items with a mean score of ≥4 (0-5) were extracted including disease activity domains and treatment/comorbidity domains. The study group provided six overarching principles for the T2T algorithm, two recommendations on treatment goals, five on evaluation of disease activity and imaging findings including positron emission tomography-computed tomography, and two on treatment intensification. CONCLUSIONS: We developed a T2T algorithm and proposals for standardised remission criteria by means of a Delphi exercise. These will guide future evaluation of different TAK treatment regimens.

Clinical features of Behçet's disease patients with joint symptoms in Japan: A national multicenter study.

OBJECTIVES: Approximately 30-60% of Behçet's disease patients exhibit joint symptoms. The aim of this study was to determine the clinical characteristics of such patients in Japan. METHODS: This study retrospectively analyzed 151 Behçet's disease patients with joint symptoms who had been treated at seven cooperative medical institutions from 2007 to 2017. We investigated their clinical characteristics and treatments. RESULTS: The most commonly affected joints were the knee, ankle, and proximal interphalangeal joints. Of the cases with pain and swelling, 18 of 293 joints (11 cases) displayed narrowing of the cleft or deformity by X-ray analysis. Improvement in their arthritis was observed in 80% of the patients who received steroids as initial treatment; however, the rate of improvement was lower in patients who had received prednisolone (PSL) at <10 mg/day. The recurrence of joint symptoms was significantly less common in the colchicine group than in the PSL group. CONCLUSIONS: These results suggest that PSL is effective for remission induction for the treatment of joint symptoms of Behçet's disease. Additionally, colchicine is effective in preventing the recurrence of joint symptoms in Behçet's disease. Furthermore, joint damages like joint space narrowing or with any deformity can often be observed in Behçet's disease.

Pregnancy outcomes in patients with rheumatoid arthritis who discontinue methotrexate treatment to conceive.

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) develops at reproductive age. Methotrexate (MTX), the anchor drug for RA treatment, is contraindicated during pregnancy. We investigated pregnancy outcomes in RA patients in whom MTX was withdrawn. METHOD: Pregnancy outcomes, RA treatment, and infertility factors were examined in patients with RA who discontinued MTX prior to attempting conception. The Mann-Whitney U test and Fisher's exact test were used to evaluate differences between the groups. RESULTS: Of the 52 patients enrolled in this study, 33 gave birth after discontinuing MTX and 19 did not. The age at MTX discontinuation was significantly different between the childbirth and non-childbirth groups (p = 0.0258). The use of non-steroidal anti-inflammatory drugs (NSAIDs) and salazosulfapyridine was significantly different between the groups (p = 0.0079 and p = 0.0438, respectively). Patients whose time from MTX discontinuation to pregnancy was longer than 12 months had a longer previous MTX administration period (p = 0.0182) and were older at the time of pregnancy (p = 0.0128) than those whose was shorter. CONCLUSIONS: The results suggest that to ensure successful childbirth in women with RA, the decision to conceive should be made at the youngest possible age, NSAIDs should not be used, and a shorter duration of MTX treatment should be considered before pregnancy. Nevertheless, additional studies with larger sample sizes are warranted to analyse the effects of other factors on pregnancies in patients with RA. KEY POINTS: • Patients with RA who plan to conceive must discontinue MTX therapy. • To achieve successful pregnancy outcomes, female patients with RA should become pregnant when they are young, discontinue NSAIDs prior to conception, and shorten their durations of MTX therapy before attempting pregnancy.

Rheumatoid arthritis relapse in patients with other iatrogenic immunodeficiency-associated lymphoproliferative disorders and its treatment.

OBJECTIVES: Rheumatoid arthritis (RA) in patients undergoing immunosuppressive therapy (IS) is sometimes involved with other iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPD). We aimed to clarify the effects of LPD treatment on RA and the current status of RA treatment options after LPD onset and subsequent IS withdrawal. METHODS: We retrospectively analyzed data of patients who had RA with LPD and examined the relationship between LPD course and RA treatment as well as that between RA relapse and LPD treatment. RESULTS: LPD patients were categorized into two groups: patients who regressed spontaneously (n = 19) and those who needed chemotherapy (n = 12). The chemotherapy group had significantly less RA relapse than the spontaneous regression group (p = .041). RA almost relapsed early in the spontaneous regression group and needed treatment for RA. Chemotherapy with rituximab prevented long-term RA relapse, and RA did not relapse for long even after rituximab monotherapy. The total dose of rituximab in monotherapy correlated with the time to RA relapse. Six patients with RA relapse received biologics and had no LPD relapse for more than 1 year. CONCLUSIONS: Rituximab in chemotherapy for LPD may help prevent RA relapse with LPD. Large-scale studies are required in the future for verification.

Lack of partial renal response by 12 weeks after induction therapy predicts poor renal response and systemic damage accrual in lupus nephritis class III or IV.

BACKGROUND: Lupus nephritis class III or IV is associated with a poor prognosis for both patient and renal survival. Recommendations for the management of lupus nephritis have recently been established, and changing therapies is recommended for patients who do not respond adequately to induction therapy. However, it remains a major challenge to determine when to switch the treatment. In this study, we identified early prognostic factors capable of predicting poor renal outcome as well as overall damage accrual in patients with lupus nephritis class III or IV. METHODS: Eighty patients with biopsy-proven lupus nephritis class III or IV were retrospectively recruited and divided into two groups: those with complete renal response (CR) or non-CR at 3 years after induction therapy. We investigated when clinical responses were obtained at each observational period from baseline to year 3. Clinical responses were divided into three groups: CR, partial renal response (PR), and non-PR. Furthermore, patients were assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and cumulative dose of corticosteroid for 3 years. RESULTS: Forty-four patients with CR and thirty-six with non-CR were enrolled. The cumulative CR rate was 85.0%. PR rates of patients with CR were significantly higher than those with non-CR from week 12 (p < 0.01). We identified the achievement of PR at 12 weeks as an independent predictor (OR 3.57, p = 0.03) by multivariate analysis. We next divided all patients into two groups according to PR achievement at week 12. The cumulative CR rate of the patients who achieved PR at week 12 was significantly higher than that of those who did not (96.5% vs 69.2%, p < 0.001). Furthermore, a significantly higher SDI and cumulative dose of corticosteroid were seen in the patients who did not achieve PR at week 12 than in those who did, regardless of their CR status, at year 3. CONCLUSIONS: Lack of PR at week 12 predicts a lower likelihood of achieving CR at 3 years and a higher SDI.

Recurrent Bilateral Focal Myositis.

This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

Psoriatic Arthritis with Annular Pustular Psoriasis.

We herein present the case of a 56-year-old woman who presented with symptoms of psoriatic arthritis (PsA) with erythema that progressed to annular pustular psoriasis. The patient had a 15-year history of polyarthritis. Annular pustular psoriasis is not typically observed in cases of arthritis. This is the first reported case of PsA with annular pustular psoriasis.

Clinical subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52.

OBJECTIVE: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52. METHODS: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed. RESULTS: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119). CONCLUSIONS: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.

Retrospective analysis of long-term outcome of chronic progressive neurological manifestations in Behcet's disease.

OBJECTIVES: Chronic progressive neuro-Behcet's disease (CPNBD) is characterized by progressive deterioration leading to disability and death. Although methotrexate has been found effective for CPNBD, its influences on the long-term outcome remain unclear. We therefore explored the effects of various treatments on the prognosis. METHODS: Thirty-seven patients, who met the international classification criteria for BD and developed chronic progressive neuropsychiatric manifestations after 1988, were followed up until October 2013. The effects of various treatments on prevention of death or severe disability of bedridden state were examined by Kaplan-Meier analysis and Cox's proportional hazard model. RESULTS: Twenty-eight of 37 patients with CPNBD (75.7%) received methotrexate. Among the 28 patients, none died and only 5 patients progressed to disability with bedridden state. By contrast, among the 9 patients without methotrexate, 5 patients died and 3 patients progressed to bedridden state. Thus, methotrexate significantly improved the survival of patients with CPNBD (HR 0.0507, p=0.020) as well as reduced the rate of progression into bedridden state or death (HR 0.2082, p=0.0126), but none of high doses of steroids, azathioprine or cyclophosphamide did. CONCLUSION: The results indicate that methotrexate, but not high doses of steroids, azathioprine or cyclophosphamide, is effective to prevent the progression of CPNBD.

Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis.

OBJECTIVES: The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m(2) for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1. RESULTS: The mean age of the 7 patients was 57 (range, 34-71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8-81) months. The mean BVAS at entry was 16.7 (range, 2-34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion. CONCLUSIONS: Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.

Assessment of the Birmingham vasculitis activity score in patients with MPO-ANCA-associated vasculitis: sub-analysis from a study by the Japanese Study Group for MPO-ANCA-associated vasculitis.

OBJECTIVES: In the study cohort enrolled in a prospective open-label, multicenter trial conducted by the Japanese Study Group for MPO-ANCA-associated vasculitis (JMAAV), we conducted this sub-analysis to establish the validity of the Birminghan vasculitis activity score (BVAS) for Japanese patients with MPO-ANCA-associated vasculitis. METHODS: We recorded the BVAS at the time of diagnosis, at 6 weeks after the diagnosis, and at 3, 6, 9, 12, 15 and 18 months after the diagnosis in this study. RESULTS: The most frequently involved organs in the patients were the lungs, kidneys and the nervous system. The kidney (BVAS; new/worse 69.2 %, persistent 40.4 %), general (BVAS; new/worse 67.3 %, persistent 53.8 %), chest (BVAS; new/worse 36.5 %, persistent 46.2 %) and nervous system (BVAS; new/worse 38.5 %, persistent 25.0 %) were the organ systems most frequently involved by the disease at the baseline. The BVAS for new/worse disease decreased immediately after induction therapy, while improvement of the BVAS for persistent disease after therapy differed among the organ systems. CONCLUSIONS: BVAS was demonstrated to be a valuable guide for selection of the optimal treatment. Thus, BVAS was also found to be a useful tool in Japanese patients for the assessment of disease activity and degree of organ damage in patients with MPO-ANCA-associated vasculitis.

Analysis of various factors on the relapse of acute neurological attacks in Behçet's disease.

OBJECTIVES: To investigate the influences of various factors on the relapse of acute neurological attacks in patients with Behçet's disease (BD). METHODS: Sixty-one patients, who met the international classification criteria for BD, had attacks of acute neuro-Behçet's disease (NBD) and could be followed up at least for 2 months, including 60 patients in our multicenter retrospective survey on BD patients in 2011. The factors associated with relapse of acute neurological attacks were assessed. RESULTS: Twenty-one of 61 patients had been taking cyclosporine A (CyA) at the onset of acute NBD. All the 21 patients with CyA and 33 of the 40 patients without CyA had eye involvement. There were no significant differences in demographic features, clinical symptoms, MRI findings, the need for, and responses to corticosteroid therapy including pulse therapy between patients with CyA and those without CyA. CyA was withdrawn in 19 of 21 patients with CyA. Of note, patients with CyA showed significantly lower relapse rates than those without CyA (HR 0.1283, 95% CI: 0.0788-0.7836, p = 0.0186 as calculated by log-rank test). Moreover, colchicine was found to reduce the relapse rates in patients with acute NBD without CyA (HR 0.2771, 95% CI: 0.0827-0.9422, p = 0.0450 [log-rank test]). CONCLUSION: These results indicate that CyA-related acute neurological manifestations are almost identical with CyA-unrelated acute events of NBD, except for the paucity of relapse on withdrawal of CyA. The data also demonstrate that colchicine is effective to prevent relapses of acute neurological attacks especially in patients with CyA-unrelated acute NBD.

Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan.

OBJECTIVE: There are differences between Europe and Japan in the incidence and antineutrophil cytoplasmic antibody (ANCA) serotype of patients with microscopic polyangiitis (MPA). However, differences in phenotype or outcome have not been explored. We aimed to identify differences in phenotype and outcome of MPA between Europe and Japan. METHODS: Sequential cohorts of patients with MPA and renal limited vasculitis were collected from European and Japanese centers (n = 147 and n = 312, respectively). Trial databases from the European Vasculitis Society and the Japanese patients with Myeloperoxidase (MPO)-ANCA-Associated Vasculitis (JMAAV) trial were studied (n = 254 and n = 48, respectively). We evaluated baseline characteristics including ANCA status and organ involvement, treatment, survival, and renal survival. Differences in survival and renal survival were studied using multivariate analysis. RESULTS: The non-trial cohorts showed patients with MPA in Japan had a higher age at onset, more frequent MPO-ANCA positivity, lower serum creatinine, and more frequent interstitial pneumonitis than those in Europe (all p < 0.01). Comparisons between the trial databases demonstrated similar results. Cumulative patient survival and renal survival rates were not different between Europe and Japan (p = 0.71 and p = 0.38, respectively). Multivariate analysis identified age at onset, serum creatinine, gastrointestinal, and respiratory involvement as factors with higher risk of death. For endstage renal failure, serum creatinine and use of plasma exchange were identified as factors with higher risk, and immunosuppressant use as lower risk factors. CONCLUSION: Phenotypes in patients with MPA were different between Europe and Japan. However, the outcomes of patient survival and renal survival were similar.

Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis.

OBJECTIVES: We aimed to identify a serum biomarker for evaluating the disease activity of relapsing polychondritis (RP). METHODS: We measured and compared serum levels of 28 biomarkers potentially associated with this disease, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), high-sensitivity C-reactive protein (hs-CRP), and cartilage oligomeric matrix protein (COMP), in 15 RP patients and 16 healthy donors (HDs). We divided the 15 RP patients into active RP (n = 8) and inactive RP (n = 7) groups, depending on the extent of the disease, and compared candidate markers between groups. The localization of membrane-bound TREM-1 in the affected tissue was examined by immunohistochemistry. RESULTS: Serum levels of sTREM-1, interferon-γ, chemokine (C-C motif) ligand 4, vascular endothelial growth factor, and matrix metalloproteinases-3 were significantly higher in RP patients than HDs. Among these markers, sTREM-1 had the highest sensitivity and specificity (86.7 and 86.7 %, respectively). Furthermore, the serum level of sTREM-1 was significantly higher in active RP patients than inactive RP patients (p = 0.0403), but this was not true for hs-CRP or COMP. TREM-1 was expressed on endothelial cells in RP lesions. CONCLUSIONS: The serum level of sTREM-1 may be a useful marker of disease activity in RP.