Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan
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PROVIDER: S-EPMC10483030 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlthough previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV.MethodsThis single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P < 0.05.ResultsDuring the median follow-up period of 19 (6-53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14-3.52, per 10 years; P = 0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5-23.0 kg/m2], adjusted HR = 2.63, 95% CI: 1.11-6.19; P = 0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07-5.76; P = 0.034) were found to be significant predictors of severe infection.ConclusionsLow BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.
| S-EPMC7942001 | biostudies-literature
Project description:BackgroundAntineutrophil cytoplasmic antibody-associated vasculitis is triggered by environmental factors, including silica dust exposure. Repeated tsunami waves brought a large volume of silica-containing sludge inland after the Great East Japan earthquake in 2011. We aimed to determine if the serious disaster influenced the clinical features of the microscopic polyangiitis.MethodsThis is an observational retrospective study conducted in a single institute. A total of 43 patients were included based on the CHCC2012 criteria for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression model to determine the incidence of microscopic polyangiitis within the annual population of the medical district. The participants were selected during a 3-year period from before (N = 13) to after the disaster (N = 20). The differences of parameters and the overall survival between the groups were analyzed.ResultsThe incidence of microscopic polyangiitis increased after the disaster (λ = 17.4/million/year [95%CI: 7.66-39.6] before the disaster and λ = 33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham Activity Score was associated with a high incidence of microscopic polyangiitis after the disaster. The overall survival of the patients with microscopic polyangiitis declined significantly after the disaster.ConclusionsThe Great East Japan earthquake influenced the development of the microscopic polyangiitis in our restricted area. The patients who developed after the disaster had severe symptoms and a high mortality rate.
| S-EPMC5428958 | biostudies-literature
Project description: Not available
| S-EPMC10658814 | biostudies-literature
Project description:Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.
| S-EPMC6506735 | biostudies-literature
Project description:BackgroundUtilizing the traditional centers of excellence approach to conduct clinical trials involving rare diseases remains challenging. Patient-based registries have been shown to be both feasible and valid in several other diseases.ObjectiveThis report outlines the clinical characteristics of a large internet registry cohort of participants with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis.MethodsPatients with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis in an internet-based prospective longitudinal cohort (from the Vasculitis Patient-Powered Research Network) were included. Data on symptoms, diagnostic testing, and treatment were collected using standardized questionnaires.ResultsThe study compared patients with granulomatosis with polyangiitis (n=762) and patients with microscopic polyangiitis (n=164). Of the cohort, 97.7% (904/925) reported the diagnosis had been confirmed by a physician. Compared to microscopic polyangiitis, patients with granulomatosis with polyangiitis reported significantly more ear, nose, and throat manifestations (granulomatosis with polyangiitis: 641/723, 88.7%; microscopic polyangiitis: 89/164, 54.3%; z=10.42, P<.001), fevers (granulomatosis with polyangiitis: 325/588, 55.3%; microscopic polyangiitis: 64/139, 46.0%; z=1.96, P=.05), joint involvement (granulomatosis with polyangiitis: 549/688, 79.8%; microscopic polyangiitis: 106/154, 68.8%; z=2.96, P=.003), and pulmonary involvement (granulomatosis with polyangiitis: 523/734, 71.3%; microscopic polyangiitis: 90/154, 58.4%; z=3.13, P=.002). Compared to microscopic polyangiitis, patients with granulomatosis with polyangiitis reported significantly less renal involvement (granulomatosis with polyangiitis: 457/743, 61.5%; microscopic polyangiitis: 135/163, 82.8%; z=-5.18, P<.001) and renal transplantation (granulomatosis with polyangiitis: 10/721, 1.4%; microscopic polyangiitis: 7/164, 4.3%; z=-2.43, P=.02). Antineutrophil cytoplasmic antibody positivity was reported in 94.2% (652/692) of patients with granulomatosis with polyangiitis and 96.1% (147/153) of patients with microscopic polyangiitis. A biopsy showing vasculitis was reported in 77.0% (562/730) of patients with granulomatosis with polyangiitis and 81.9% (131/160) of patients with microscopic polyangiitis.ConclusionsIn this large, internet-based cohort of patients with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, disease manifestations were consistent with expectations for each type of vasculitis. Given the rarity of these and other vasculitides, conducting some types of research through internet-based registries may provide an efficient alternative to inperson, center-of-excellence clinical trials.
| S-EPMC7428147 | biostudies-literature
Project description:To explore disease characteristics, renal involvement and induction treatment strategies over the last decades and evaluate relapse rates and renal outcomes in ANCA-associated vasculitides (AAV). We retrospectively analyzed remission, relapse rates and the occurrence of the composite endpoint (comprising death and renal failure) in newly diagnosed AAV cases in four tertial referral centers in Germany and Switzerland diagnosed between 1999 and 2022. Hazard ratios were computed by Cox proportional hazard and Kaplan-Meier curves were plotted to compare therapeutic strategies after propensity-matching. In our cohort of 358 AAV patients, 203 (58.1%) were classified as granulomatosis with polyangiitis (GPA) based on the novel 2022 ACR/EULAR criteria, 139 (38.8%) as microscopic polyangiitis (MPA). The proportion of MPA cases among all AAV patients increased from 28.9% between 1999 and 2013 up to 46.7% thereafter. Cyclophosphamide (CYC) was chosen most frequently for remission induction (74.8% before 2013 and 57.3% thereafter), whereas the use of rituximab (RTX) increased from 5 to 26% within these periods. GPA patients had a higher relapse rate as compared to MPA patients (41.3% vs. 25.9%, p = 0.006). However, in AAV patients with renal involvement, renal events (i.e. end-stage kidney disease or a persistent drop in the estimated glomerular filtration rate (eGFR) below 15 ml/min/1.73 m2) occurred more frequently in MPA patients, particularly under RTX treatment as compared to matched CYC counterparts (11.8% vs. 7.5%, p = 0.011). In our cohort, GPA patients exhibited frequent relapses, advocating for a more intense and extended treatment. MPA patients had lower relapse rates, however, RTX was less effective to prevent renal endpoints in MPA as compared to CYC, highlighting the need to further investigate additional treatment strategies.
| S-EPMC11668861 | biostudies-literature
Project description:The antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAVs), which include fever of unknown origin (FUO), are rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCAs. Microscopic polyangiitis (MPA) is a subtype of the AAVs. Although the prevalence of AAVs has generally increased over the last 20 years, there have been rare reports from the dental and oral surgery field. In this article, we present a case of MPA suspected to be infective endocarditis (IE) following tooth extraction.
| S-EPMC7102490 | biostudies-literature
Project description:ObjectiveThe present study was undertaken to conduct a phase IV, open-label, prospective study to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the US.MethodsPatients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes included the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies.ResultsOverall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range 1-28) infusions and were followed up for a median of 3.94 years (range 0.05-4.32 years). The estimated incidence rates (95% confidence interval [95% CI]) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55-10.58), 5.03 (2.93-8.06), and 2.37 (1.02-4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate 2.67 [95% CI 1.22-5.06] per 100 PYs) were considered to be related to use of rituximab.ConclusionThe safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune diseases for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA.
| S-EPMC8457173 | biostudies-literature
Project description:To search for new markers of active lesions that might help better understand the molecular basis of MPA and aid in its diagnosis, DNA microarray analysis was performed with peripheral blood mononuclear cells (PBMCs).
2013-08-18 | GSE41744 | GEO
Project description:The epidemiology of ANCA-associated vasculitis is substantially different between Caucasians and Japanese, which may be related to differences in genetic backgrounds. In this review, I discussed our findings on the genetics of microscopic polyangiitis (MPA) in Japanese. Analysis of HLA genes revealed a significant increase in the HLA-DRB1*09:01-DQB1*03:03 haplotype MPA. This is one of the most frequent haplotypes in Japanese, but is nearly absent in Caucasians, and has been shown to be associated with multiple autoimmune diseases. Analysis of KIR genes revealed significant decreases in the carrier frequency of an activating receptor KIR2DS3 in MPA. When KIRs were analyzed in combination with HLA ligands, the proportion of individuals carrying KIR3DL1 and HLA-Bw4 but not KIR3DS1, the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in MPA. These results suggested that decreased activation of NK and/or T cells may cause a predisposition to MPA. LILRA2 is an activating receptor involved in granulocyte and macrophage activation. LILRA2 SNP rs2241524 G >A, which disrupts the intron 6 splice acceptor site, was significantly associated with MPA. The risk allele produces an LILRA2 isoform lacking three amino acids in the linker region. These findings, when confirmed by larger-scale studies, will shed light on the molecular mechanisms of MPA. (*English Translation of J Jpn Coll Angiol 2009; 49: 31-37.).
| S-EPMC3595849 | biostudies-literature