High plasma mycophenolate acid concentration in the early phase of induction therapy predicts good renal outcome in lupus nephritis.

Objectives: To identify the prognostic predictive factor of complete renal response (CR) at week 12 by focusing on the plasma mycophenolic acid (MPA) concentration in induction therapy in lupus nephritis.Methods: We prospectively enrolled patients with biopsy-proven LN class III/IV who were hospitalized between 2016 and 2017. As an induction therapy, mycophenolate mofetil was continuously introduced at 2000 mg/day. We measured the MPA plasma concentration at two time points depending on the induction therapy phase, early (week 4) or middle (week 12). The association between these concentrations and CR rate at week 12 was evaluated.Results: Ten patients were enrolled. A significantly higher AUC0-12 between 0 and 12 h of MPA at the early phase was observed in the patients with CR at week 12 than in those without (p = .03). All the patients with high MPA-AUC0-12 (> 40 mg h/L) at the early phase achieved CR at week 12, but no such association was found at the middle phase. The multivariate analysis revealed that MPA-AUC0-12 was selected as an independent predictive factor of CR at week 12 (odds ratio: 1.12; 95% confidence interval: 1.01-1.45, p = .02).Conclusion: The high AUC0-12 of MPA at the early phase of induction therapy may predict good renal response.

Association of ETS1 polymorphism with granulomatosis with polyangiitis and proteinase 3-anti-neutrophil cytoplasmic antibody positive vasculitis in a Japanese population.

ETS proto-oncogene 1, transcription factor (ETS1) is involved in various immune responses. Genome-wide association studies on systemic lupus erythematosus in Chinese populations identified the association of ETS1 polymorphism in 3' untranslated region, rs1128334A, which was associated with lower ETS1 expression. In view of substantial sharing of susceptibility genes across multiple autoimmune diseases, we examined whether ETS1 is associated with a rare autoimmune rheumatic disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099 healthy controls by logistic regression analysis under the additive model. AAV patients were classified into 285 microscopic polyangiitis (MPA), 92 granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33 unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm. Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. When the patients were classified according to the EMEA classification, rs1128334A allele was significantly increased in GPA (P = 0.0060, P c = 0.030, odds ratio (OR), 1.54; 95% confidence interval (CI), 1.13-2.10). With respect to the ANCA specificity, significant association was observed in PR3-ANCA positive AAV (P = 0.0042, P c = 0.021, OR, 1.72; 95% CI, 1.19-2.49). In conclusion, ETS1 polymorphism was suggested to be associated with GPA and PR3-ANCA positive AAV in a Japanese population.

Combined disease with pulmonary arterial hypertension and pulmonary venous hypertension revealed after treatment of heart failure with preserved ejection fraction in a case with primary Sjögren syndrome.

A 49-year-old woman with primary Sjögren syndrome initially developed pulmonary venous hypertension (PVH) due to heart failure with preserved ejection fraction. Endomyocardial biopsy specimens showed mild myocardial fibrosis. Pulmonary arterial hypertension (PAH) was revealed after the treatment with diuretics. During the treatment for PAH using upfront combination with pulmonary vasodilators and immunosuppressants, the patient developed combined disease with PAH and PVH. A careful hemodynamic assessment is necessary in such cases.

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.

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.

Left heart abnormalities in connective tissue disease patients with pre-capillary pulmonary hypertension as well as borderline mean pulmonary arterial pressure.

OBJECTIVE: To describe co-existence of left heart abnormalities among case series of connective tissue disease (CTD) patients who showed pre-capillary pulmonary hypertension (PH) as well as borderline mean pulmonary arterial pressure (mPAP). METHODS: From 2010 through 2012, 49 CTD patients suspected to have PH by exercise Doppler echocardiography underwent right heart catheterization. We retrospectively searched for left heart diseases from the available data on Doppler echocardiography, cardiac magnetic resonance imaging (MRI), scintigraphy, and endomyocardial biopsy. RESULTS: Among 49 patients, 11 and 2 had pre- and post-capillary PH, respectively, and another 10 had borderline mPAP. Six of 11 patients with pre-capillary PH showed low pulmonary vascular resistance (PVR) (≤ 240 dynes•sec•cm(- 5)) and low diastolic pulmonary gradient (< 7 mmHg). Seven of 10 patients with borderline mPAP had normal PVR (< 160) suggesting the presence of left heart abnormalities. Other abnormal findings included increased left atrial volume index and E/E' on Doppler echocardiography, delayed contrast enhancement by MRI, patchy area of hypoperfusion on thallium scintigraphy, and fibrosis in endomyocardial biopsy. CONCLUSION: The present case series suggested some contribution of left heart abnormalities to the increase in mPAP among CTD patients with pre-capillary PH as well as borderline mPAP.

Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behçet's disease.

OBJECTIVES: To investigate the pathophysiology of Behçet's disease (BD) and find biomarkers for the disease, we analysed protein profiles of peripheral blood mononuclear cells (PBMCs). METHODS: Proteins, extracted from PBMCs, were comprehensively analysed in 16 patients with BD, 16 patients with rheumatoid arthritis (RA), 12 patients with Crohn's disease (CD), and 16 healthy control subjects (HC) by 2-dimensional differential gel electrophoResis (2D-DIGE). Differently expressed proteins were identified by mass spectrometry. RESULTS: 563 protein spots were detected. We completely discriminated between the BD and HC groups, between the BD and RA groups, and between the BD and CD groups by multivariate analysis of intensity of 23, 35, and 1 spots, respectively. The spots contributing to the differences included proteins related to cytoskeleton, transcription/translation, T cell activation, bone turnover, regulating apoptosis, and microbial infection. Intensity of 3 spots (tyrosine-protein phosphatase non-receptor type 4, threonine synthase-like 2, and ß-actin) provided area under the receiver operating characteristic curves (AUROC) of 0.889 for discrimination between the BD group and the non-BD groups. Informatively, intensity of the above 1 spot completely discriminated the CD group from the other groups (AUROC 1.000). This spot, identified as ß-actin, had different pI from the above ß-actin-spot probably due to different post-translational modification. CONCLUSIONS: PBMC protein profiles, especially the profile of the 3 spots, would be candidate biomarkers for BD. The latter ß-actin subtype would be useful for discriminating inflammatory bowel diseases from BD and other diseases. The identified proteins may play important roles in the pathophysiology of BD.

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.

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.

Clinical trial for Japanese patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis: the JMAAV study.

In view of the marked difference in epidemiology of myeloperoxidase/proteinase 3 anti-neutrophil cytoplasmic antibody (MPO/PR3-ANCA)-associated vasculitis between Japan and Western countries, a prospective, open-label, multi-center trial (Japanese Patients with MPO-ANCA-Associated Vasculitis; JMAAV) was performed to evaluate the usefulness of severity-based treatment in Japanese patients with newly diagnosed MPO-ANCA-associated vasculitis. Among the 47 patients enrolled and prescribed predefined therapies, 42 achieved remission within 6 months (89%), 5 died (11%), and 1 developed end-stage renal disease (2%). Disease relapsed in 8 of the 42 patients with remission during the 18-month follow-up period (19%). The remission and death rates were comparable to several previous clinical trials performed in Western counties. Relapse and severe infection, however, appeared to be more frequent than in previous trials, and therefore should be investigated further in future trials. Subsidiary analysis was also performed using samples from these patients, and a new serum biomarker for microscopic polyangiitis and a novel gene expression profile of peripheral blood to predict response to treatment were found by proteomic and transcriptomic analysis, respectively.

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.

Tolerability and efficacy of abatacept in Japanese patients with rheumatoid arthritis: a phase I study.

OBJECTIVE: The primary objective of this study was to evaluate the tolerability of single and multiple doses of abatacept in Japanese patients with rheumatoid arthritis. Secondary objectives included evaluating its pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy. METHODS: This dose-escalation, single- and multiple-dose, multicenter, open-label study was conducted at nine sites in Japan. Seven patients were enrolled at each of three dose levels (2, 8 and 16 mg/kg) and received a single intravenous dose of abatacept on day 1 of the single-dose phase. The multiple-dose phase, at the same dose, started once the patients had completed the single-dose phase and when it was confirmed that there were no safety issues. RESULTS: Twenty patients started the single-dose phase. Single and multiple doses of abatacept were well tolerated, and adverse events were of mild to moderate intensity. There were no discontinuations or deaths due to adverse events. The pharmacokinetics of abatacept were linear, with no notable accumulation. There were no immunogenic effects on the safety, efficacy, or pharmacokinetics of abatacept. Multiple doses of abatacept improved individual items of the American College of Rheumatology core set. CONCLUSION: Single and multiple doses of abatacept showed favorable tolerability and efficacy in Japanese patients with rheumatoid arthritis.

Hypoxia-induced endogenous prostaglandin E2 negatively regulates hypoxia-enhanced aberrant overgrowth of rheumatoid synovial tissue.

OBJECTIVE: During isometric exercise, the synovial joint tissue is prone to hypoxia, which is further enhanced in the presence of synovial inflammation. Hypoxia is also known to induce inflammatory cascades, suggesting that periodic hypoxia perpetuates synovitis in rheumatoid arthritis. We previously established an ex vivo cellular model of rheumatoid arthritis using the synovial tissue-derived inflammatory cells, which reproduced aberrant synovial overgrowth and pannus-like tissue development in vitro. Using this model, we investigated the regulatory mechanism of synovial cells against hypoxia in rheumatoid arthritis. METHODS: Inflammatory cells that infiltrated synovial tissue from patients with rheumatoid arthritis were collected without enzyme digestion, and designated as synovial tissue-derived inflammatory cells. Under normoxia or periodic hypoxia twice a week, their single-cell suspension was cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Cytokines produced in the culture supernatants were measured by enzyme-linked immunosorbent assay kits. RESULTS: Primary culture of the synovial tissue-derived inflammatory cells under periodic hypoxia resulted in the attenuation of the spontaneous growth of inflammatory tissue in vitro compared to the culture under normoxia. Endogenous prostaglandin E2 (PGE2) production was enhanced under periodic hypoxia. When endogenous PGE2 was blocked by indomethacin, the aberrant tissue overgrowth was more enhanced under hypoxia than normoxia. Indomethacin also enhanced the production of tumor necrosis factor-α (TNF-α), macrophage colony-stimulating factor (M-CSF), and matrix metalloproteinase-9 (MMP-9) under periodic hypoxia compared to normoxia. The EP4-specific antagonist reproduced the effect of indomethacin. Exogenous PGE1 and EP4-specific agonist effectively inhibited the aberrant overgrowth and the production of the inflammatory mediators under periodic hypoxia as well as normoxia. CONCLUSIONS: The enhancing effect of periodic hypoxia on the aberrant overgrowth of rheumatoid synovial tissue was effectively down-regulated by the simultaneously induced endogenous PGE2.

A novel anti-peroxiredoxin autoantibody in patients with Kawasaki disease.

Antibodies to the anti-oxidative peroxiredoxin (Prx) enzymes occur in both systemic autoimmune disease and vasculitis in adulthood. Because increased oxidative stress induces vasculitis in Kawasaki disease (KD), autoimmunity to Prxs in patients with KD was investigated. The presence of antibodies to Prx 1, 2 and 4 was analyzed by ELISA and Western blot. Of 30 patients with KD, 13 (43.3%) possessed antibodies to Prx 2, whereas these antibodies were present in only 1 of 10 patients (10.0%) with sepsis (4 with purulent meningitis and 6 with septicemia). In contrast, antibodies to Prx 1 and 4 were not detected in either group. There was no significant correlation among the titers of the three antibodies. Clinical parameters were compared between anti-Prx 2-positive and -negative patients. The presence of anti-Prx 2 antibodies correlated with a longer period of fever and poor response to high-dose γ-globulin therapy in patients with KD. Anti-Prx 2-positive patients had significantly greater excretion of urinary 8-isoprostaglandin than did anti-Prx 2-negative patients. These results provide the first evidence for an antibody to Prx 2 in patients with KD. They also suggest that this antibody might serve as a marker of disease severity and be involved in the pathophysiology of vasculitis in some patients with KD.

Endogenous prostaglandin E2 inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor.

OBJECTIVE: We recently developed an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue. This study was undertaken to use that model to investigate the role of prostaglandin E2 (PGE2) and its receptor subtypes in the development of pannus growth and osteoclast activity in rheumatoid arthritis (RA). METHODS: Inflammatory cells that infiltrated pannus from patients with RA were collected without enzyme digestion and designated synovial tissue-derived inflammatory cells. Their single-cell suspensions were cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by the development of resorption pits in calcium phosphate-coated slides. RESULTS: Primary culture of the synovial tissue-derived inflammatory cells resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during which tumor necrosis factor α, PGE2, macrophage colony-stimulating factor, and matrix metalloproteinase 9 were produced in the supernatant. This aberrant overgrowth was inhibited by antirheumatic drugs including methotrexate and infliximab. On calcium phosphate-coated slides, synovial tissue-derived inflammatory cells showed numerous resorption pits. In the presence of inhibitors of endogenous prostanoid production such as indomethacin and NS398, exogenous PGE1 and EP4-specific agonists significantly inhibited all these activities of synovial tissue-derived inflammatory cells in a dose-dependent manner. Addition of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of these cells' activities. EP2-specific agonist had a partial effect, while EP1- and EP3-specific agonists had no significant effects. CONCLUSION: These results suggest that endogenous PGE2 produced in rheumatoid synovium negatively regulates aberrant synovial overgrowth and the development of osteoclast activity via EP4.

AC13, a C-terminal fragment of apolipoprotein A-I, is a candidate biomarker for microscopic polyangiitis.

OBJECTIVE: Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease. METHODS: Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg-Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. RESULTS: A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C-terminal amino acid residues of apolipoprotein A-I (Apo A-I) and was designated "AC13." Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A-I and high-density lipoprotein cholesterol were down-regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up-regulated secretion of interleukin-6 (IL-6) (P < 0.05) and IL-8 (P < 0.01). CONCLUSION: AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up-regulation of proinflammatory cytokines.

Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study.

OBJECTIVES: To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone. METHODS: According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18 months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients. RESULTS: The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18 months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional. CONCLUSION: MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL.

Cutaneous polyarteritis nodosa associated with HLA-B39-positive undifferentiated spondyloarthritis in a Japanese patient.

We present the case of a 43-year-old man diagnosed with HLA-B39-positive spondyloarthritis who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa (CPN). Previous studies indicated an elevated incidence of HLA-B39 in HLA-B27-negative Japanese patients with spondyloarthritis. This case suggested that CPN may also occur in association with forms of HLA-B39-positive spondyloarthritis. The rarity of this association is emphasized. Therapy with corticosteroid and methotrexate improved both the cutaneous lesions and the clinical symptoms of spondyloarthritis.