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Objectives: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry., Methods: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019., Results: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%)., Conclusions: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Objectives: To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea., Methods: We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit., Results: We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA., Conclusions: In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

Background: The epidemiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) varies worldwide. Previous Australian studies described a higher incidence of AAV in rural areas; however, this has not yet been investigated in Victoria., Aims: To calculate the incidence of AAV in rural and regional Victoria and characterise the demographics and clinical outcomes of this cohort., Methods: We performed a retrospective review of patients with newly diagnosed AAV confirmed on renal biopsy at Bendigo Health between 2013 and 2021. Cases were classified according to the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. Local disease incidence was calculated using Estimated Resident Population data for our catchment, the Loddon Mallee region., Results: Twenty-eight cases of new AAV were identified; 17 were classified as microscopic polyangiitis (MPA) and the remainder as granulomatosis with polyangiitis (GPA). The median age at diagnosis was 68 years (interquartile range (IQR): 59-77). The incidence per million person-years was 9.3 for AAV overall (95% CI: 6.2-13.5), 5.7 for MPA (95% CI: 3.3-9.1) and 3.7 for GPA (95% CI: 1.8-6.6). With a median follow-up time of 3.3 years (IQR: 1.9-5.6), one-quarter of patients relapsed (n = 7, 25%), and six required ongoing renal-replacement therapy (21%)., Conclusions: The calculated incidence of AAV in rural and regional Victoria is not higher than the reported incidence in most urban Australian cohorts. This study may underestimate the true local disease incidence as only patients with renal vasculitis were included., (© 2023 Royal Australasian College of Physicians.)

Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden., Methods: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code)., Results: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations., Conclusion: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression., (© 2023. The Author(s).)

Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

ANCA-associated vasculitides (AAV) are rare, complex systemic diseases that are often difficult to diagnose, because of unspecific clinical symptoms at presentation. However, the clinical course may be very dramatic and even life-threatening, necessitating prompt diagnosis and treatment.Therefore, it is important to increase disease awareness among physicians and support colleagues who are not confronted with these rare diseases on a regular basis. Here, the Austrian Society of Nephrology (ÖGN) and the Austrian Society of Rheumatology (ÖGR) provide a joint consensus on how to best diagnose and manage patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)., (© 2023. The Author(s).)

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders with alternating periods of relapse and remission. Beyond that, a smouldering progress during apparently clinically silent phases often develops. AAVs are subgrouped in microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and renal limited vasculitis (RLV). ANCA are hallmark of this disease entity, although they are not always present. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. Through the advances in pathogenesis and pathophysiology of AAV a reliable biomarker-based monitoring and treatment algorithm has not been established and disease management follows not infrequently a "trial and error" approach. Here, we overviewed the most interesting biomarkers reported so far., (© 2023 The Scandinavian Foundation for Immunology.)

Objective: To update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden., Methods: The study area comprised 14 municipalities with a combined adult population (≥18 years) of 623 872 in 2019. All cases diagnosed with AAV in 1997-2019 in the study area were included in the estimate of incidence. Diagnosis of AAV was verified by case record review, and cases were classified using the European Medicines Agency algorithm. Point prevalence was estimated on 01 January 2020., Results: Three hundred and seventy-four patients (median age 67.5 years, 47% female) were diagnosed with new-onset AAV during the study period. One hundred and ninety-two were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as EGPA. The average annual incidence/million adults was 30.1 (95% CI 27.0 to 33.1) for AAV: 15.4 (95% CI 13.3 to 17.6) for GPA, 12.8 (95% CI 10.8 to 14.8) for MPA and 1.8 (95% CI 1.1 to 2.6) for eosinophilic GPA (EGPA). Incidence was stable during the study period, 30.3/million 1997-2003, 30.4/million 2004-2011 and 29.5/million 2012-2019. The incidence increased with age and was highest in age group 70-84 years (96/million adults). On 1 January 2020, the prevalence was 428/million adults and was higher in males than in females (480 vs 378/million)., Conclusions: The incidence of AAV in southern Sweden was found stable over the course of 23 years; while the prevalence has increased, which might indicate better management and treatment of AAV resulting in improved survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Diffuse alveolar hemorrhage (DAH) is associated with high mortality. We examined the efficacy of plasma exchange (PE) therapy for reducing mortality in patients with patients with microscopic polyangiitis (MPA) and DAH., Methods: In this 52-week, nonrandomized, open-label, one-arm, historical control, double-center controlled trial, four patients with MPA and DAH admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between 2018 and 2021 were enrolled. Sixteen patients with MPA and DAH admitted to the two centers between 1998 and 2018 who did not receive PE were included as the historical control group. The primary outcome was the 52-week survival rate of patients in each treatment arm., Results: The 52-week survival rate of patients in the PE group (n = 4) was higher than that of the historical control group (n = 16) (100% vs. 13%, p = 0.04)., Conclusion: We found that PE may be efficacious for reducing mortality in patients with MPA and DAH., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Background/objective: Antineutrophil cytoplasmic antibody-associated vasculitides (AAVs) are uncommon systemic autoimmune diseases, of which few reports exist in Latin America. Our aim was to examine AAV evaluated in a high-complexity hospital in southwestern Colombia, with emphasis in severe forms., Methods: A medical records review study of 67 patients was performed, and data were collected from electronic registries. Moderate and severe AAVs were defined as the presence of life-threatening complications, unfavorable Birmingham Vasculitis Activity Score outcomes, and hospitalization requirements at the time of diagnosis and by the last follow-up, between 2011 and 2019. Clinical manifestations, treatment, and outcomes were evaluated. The AAV subtypes were compared., Results: A total of 67 cases were included. The majority were female (n = 44, 65.67%), and the median age was 52 (40-64) years. Granulomatosis with polyangiitis (GPA) was the most frequent with 42 patients (62.68%), followed by microscopic polyangiitis (MPA) and eosinophilic GPA, with 15 patients (22.38%) and 10 patients (14.92%), respectively. Forty-four patients (65.67%) presented pulmonary symptoms. The highest Birmingham Vasculitis Activity Score corresponded to MPA, with 21 (12-25) points. Fifteen patients (22.4%) were admitted to the intensive care unit throughout the course of the disease, of whom 10 had GPA. The longest stay and duration of mechanical ventilation were seen in MPA. The principal treatments were corticosteroids and cyclophosphamide, and the main outcome was end-stage renal disease., Conclusions: In this cohort of AAV, most of cases corresponded to GPA, and pulmonary manifestations were the most common. Microscopic polyangiitis was the more severe subtype as it showed worse impairment in clinical characteristics and intensive care unit requirements., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: ANCA-associated vasculitis (AAV) is an infrequent disease in childhood. International literature about pediatric vasculitis is scarce, and it mainly refers to other systemic vasculitides with a higher incidence in childhood, such as IgA vasculitis and Kawasaki disease., Objective: To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV., Patients and Method: Re trospective, descriptive study of patients with diagnosis of AAV treated at a tertiary health center from Santiago, Chile, between 2000 and 2020. Electronic medical records were reviewed collecting epidemiological, laboratory, images, and biopsies data., Results: There were five cases of pediatric pa tients with AAV, with varying degrees of severity, and the age range at the onset was 5.5 to 13.5 years. We observed frequent renal involvement in microscopic polyangiitis (MPA) and eye involvement due to orbital pseudotumor in patients with granulomatosis with polyangiitis (GPA), an infrequent manifestation in the international pediatric literature. Patients were treated according to recommen dations extrapolated from clinical trials in adult populations, showing excellent clinical response to induction therapy with systemic corticosteroids and cyclophosphamide or rituximab. During main tenance therapy, most of the patients were stable on rituximab, azathioprine, or methotrexate. No patient developed organ damage and all cases achieved discontinuation of the corticosteroid therapy., Conclusion: This report describes the clinical characteristics of AAV in a series of pediatric patients. In this series, renal involvement was common in MPA and eye involvement due to orbital pseudotu mor in GPA. The clinical response with treatment according to recommendations extrapolated from the adult population was favorable.

Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

There have been great advances in the management of ANCA associated vasculitis over the past decades. We have gone from an era where the disease was almost universally fatal to trying to prevent long-term side effects of treatment regimens. With the ability to use pulse cyclophosphamide or rituximab as alternates to oral cyclophosphamide for induction of remission, side effects of therapy have been greatly reduced. New approaches have drastically changed our approach to maintenance and we now favor much longer durations of maintenance therapy, as they are more successful in preventing relapse. Steroids have long been the bane of treatment as they are associated with a significant risk of infection and metabolic consequences. We are now in a steroid-sparing and looking ahead to a steroid-free era with new data being published showing lower doses of steroids being equally effective and several ongoing seminal trials looking at agents that could completely replace steroids very early on., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To describe characteristics and long-term outcomes of patients with microscopic polyangiitis (MPA), an antineutrophil cytoplasm antibody (ANCA)-associated small-vessel necrotizing vasculitis., Methods: MPA patients from the French Vasculitis Study Group Registry satisfying the European Medicines Agency algorithm were analyzed retrospectively. Characteristics at diagnosis, treatments, relapses and deaths were analyzed to identify factors predictive of death or relapse., Results: Between 1966 and 2017, 378 MPA patients (median age 63.7 years) were diagnosed and followed for a mean of 5.5 years. At diagnosis, the main clinical manifestations included renal involvement (74%), arthralgias (45%), skin (41%), lung (40%) and mononeuritis multiplex (32%), with less frequent alveolar hemorrhage (16%), cardiomyopathy (5%) and severe gastrointestinal signs (4%); mean serum creatinine was 217 μmol/L. ANCA were detected in 298/347 (86%) patients by immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA). Among the 293 patients with available ELISA specificities, 272 (92.8%) recognized myeloperoxidase and 13 (4.4%) proteinase-3. During follow-up, 131 (34.7%) patients relapsed and 78 (20.6%) died, mainly from infections. Respective 5-year overall and relapse-free survival rates were 84.2% and 60.4%. Multivariable analyses retained age >65 years, creatinine >130 μmol/L, severe gastrointestinal involvement and mononeuritis multiplex as independent risk factors for death. Renal impairment was associated with a lower risk of relapse., Conclusion: Non-renal manifestations and several risk factors for death or relapse were frequent in this nationwide cohort. While mortality was low, and mainly due to treatment-related complications, relapses remained frequent, suggesting that MPA management can be further improved., Competing Interests: Declaration of competing interest Dr. Pagnoux reports grants and personal fees from Roche, personal fees from ChemoCentryx, grants and personal fees from GSK, personal fees from Sanofi, outside the submitted work; Dr. Puéchal reports non-financial support from Roche, non-financial support from ChemoCentryx, non-financial support from InflaRx, personal fees and non-financial support from Sanofi, personal fees from Boehringer Ingelheim, non-financial support from GSK, outside the submitted work; All other authors have nothing to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double-center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non-disease-specific mortality. The 1-year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five-Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Pulmonary vasculitis is a group of rapidly progressing severe diseases characterized by vascular inflammation, destruction and necrosis of the pulmonary tissue. The pathological process in the lungs varies from diffuse alveolar hemorrhage to inflammation of the parenchyma, pleural effusion, thrombotic and thromboembolic complications. Depending on the size of the affected vessels, vasculites are divided into vasculites of large, medium and small vessels. Most frequently the lung is found in the small vessels vasculitis, including ANCA-associated vasculitis [granulomatosis with polyangiitis (GP), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA)] and the disease is glomerular basement membrane (goodpasture syndrome). Clinical examination of other systems and organs involved in the pathological process, including the skin and kidneys, as well as the detection of autoantibodies can improve approaches to early diagnosis and treatment of vasculitis. Treatment of life-threatening pulmonary bleeding and irreversible damage to organs, especially the kidneys, requires rapid diagnosis of these conditions. Vasculitis is a rare disease with lesions of many organs, and methods of their treatment, including biological, are rapidly developing, which requires the cooperation of doctors of various specialties and specialized centers to achieve better control of the disease.

Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively. All patients with available C3 and C4 levels at diagnosis were included. Patients were categorized in the hypocomplementemia group if their C3 and/or C4 levels at diagnosis were below the lower limit of the normal range. Among the 76 AAV patients (43 GPA, 33 MPA), 4 (5%) had hypocomplementemia, and the 72 remaining patients exhibited normal plasma complement levels. All 4 hypocomplementemia patients had renal involvement. Hypocomplementemia was followed in 1 patient whose post-treatment complement level normalized within 1 month. Among all clinical and ANCA specificity, including relapse-free survival (p = 0.093), only overall and renal survival rates were significantly lower in the hypocomplementemia group (p = 0.0011 and p<0.001, respectively). Hypocomplementemia with low C3 and/or C4 levels at GPA or MPA diagnosis may be responsible for worse survival and renal prognosis. These results argue for larger and prospective studies to better determine the epidemiology of the disease and to assess complement-targeting therapy in these patients.

Case Description: A 16 year-old female who presented with initial ear, nose and throat manifestations who later progressed to severe renal disease, requiring hemodialysis after 11 months of unique laryngeal involvement., Clinical Findings: Unilateral vocal cord paralysis without other symptoms or signs, but with positive perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase autoantibodies, followed an unfavorable course months later with rapidly progressive glomerulonephritis. Renal biopsy confirmed an ANCA-associated vasculitis. She was diagnosed with microscopic polyangiitis., Treatment and Outcome: High-dose glucocorticoids, intravenous cyclophosphamide, plasma exchange and finally, hemodialysis and renal transplantation., Clinical Relevance: In contrast to granulomatosis with polyangiitis (Wegener), ear, nose and throat manifestations in microscopic polyangiitis are uncommon, while involvement of the lungs and kidneys are usual. We present a case with an isolated rare involvement, which progressed to severe disease. This atypical case warns about laryngeal symptoms as initial manifestation of an anti-myeloperoxidase positive systemic vasculitides, and emphasizes the relevance of close observation when unexplained isolated conditions with accompanying evidence of autoimmunity, in this case high levels of specific autoantibodies, are present.

Objectives: We investigated whether specified organ involvements, antineutrophil cytoplasmic antibody (ANCA) positivity, Birmingham vasculitis activity score (BVAS) and five factor scores (FFS) at diagnosis could predict relapse of microscopic polyangiitis (MPA)., Methods: We reviewed the medical records of 90 patients with MPA. We collected clinical and prognostic data, (MPO)-ANCA and proteinase 3 (PR3)-ANCA, BVAS and FFS at diagnosis, and we compared them between the two groups. The optimal cut-off values of BVAS and FFS (1996) for predicting relapse were extrapolated., Results: The mean age of patients (63 women) was 62.3 years and the mean follow-up duration was 41.7 months. At diagnosis, the mean BVAS, FFS (1996) and FFS (2009) of patients in no remission group were higher than those of patients in remission group (p<0.005 for all). Patients in relapse group exhibited chest and renal manifestations more frequently than those in no relapse group and the mean BVAS and FFS (1996) of patients in relapse group were significantly higher than those of patients in remission group (p<0.005 for all). There were no differences in MPO-ANCA and PR3-ANCA between the two groups. On multivariate logistic regression analysis, chest and renal manifestations were all independent predictors of relapse (OR 2.013 and OR 3.517). Patients who had BVAS ≥13.5 and FFS ≥ 1 exhibited a significantly increased risk of relapse than those who did not (RR 4.408 and RR 3.030)., Conclusions: Chest and renal involvements, BVAS ≥13.5 and FFS ≥1 at diagnosis were independent predictors of relapse of MPA.

Objectives: We reclassified Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) into 3 categories of AAV including MPO-ANCA, PR3-ANCA and ANCA-negative vasculitis, and investigated clinical and prognostic features., Methods: We reviewed the medical records of 133 patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA), who had either myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCA or no ANCA, and who had ever achieved the first remission. We compared clinical manifestations, initial Birmingham vasculitis activity score (BVAS) and five factor score (FFS), and relapse rates., Results: Patients with ANCA-negative vasculitis had the youngest mean age at diagnosis (50.0 years old) among AAV categories. General, cutaneous and renal manifestations were commonly observed in MPO-ANCA vasculitis, while mucous membrane, eye, ear nose throat (ENT) and renal manifestations were often documented in PR3-ANCA vasculitis. ENT manifestation was also frequently observed in ANCA-negative vasculitis. However, there were no significant differences in pulmonary and nervous system manifestations among 3 AAV categories. There were no significant differences in cumulative relapse free survival according to the presence of MPO-ANCA or PR3-ANCA or no ANCA. Meanwhile, initial BVAS or BVAS for GPA ≥13.5 in MPO-ANCA vasculitis and initial FFS (1996) ≥1 in MPO-ANCA and ANCA-negative vasculitis were significant predictors of relapse of each AAV category., Conclusions: Clinical manifestations varied AAV categories, and neither MPO-ANCA nor PR3-ANCA significantly affected relapse of AAV. Initial BVAS or BVAS for GPA and FFS (1996) helped to predict relapse of specified AAV categories.

Background: The evidence of the benefit of plasmapheresis in renal and survival outcomes in patients with severe manifestations of ANCA-associated vasculitides is inconsistent., Purpose: To address whether plasmapheresis is associated with improvement in renal function and survival at 12 months in patients with severe manifestations of ANCA-associated vasculitides., Patients and Methods: Single-center retrospective comparative cohort of 24 patients with granulomatosis with polyangiitis or microscopic polyangiitis that received plasmapheresis adjunctive to conventional therapy (steroids and immunosuppressants), matched 1:1 according to age, estimated glomerular filtration rate (eGFR) and disease activity with 24 patients treated with standard treatment only. Comorbidities, demographic, clinical, treatment and laboratory characteristics were recorded., Results: After 12 months both groups showed improvement in eGFR (19.0 ± 14.34 to 41.61 ± 37.77 ml/min, p = 0.003 in plasmapheresis group; 23.16 ± 14.71 to 39.86 ± 25.67 ml/min, p = 0.001 in conventional therapy group). No differences were found between groups (p = 0.68). Patients free of dialysis at 12 months after intervention increased in the plasmapheresis group from 9/24 (38%) to 12/24 (50%), p = 0.5; and in the conventional therapy group from 19/24 (79%) to 22/24 (92%), p = 0.25. Difference between groups was significant at 12 months (p = 0.001). Survival at 12 months after intervention was 79% in the plasmapheresis group and 96% in the conventional therapy group (p = 0.08). The main cause of death was infectious and a tendency for a higher prevalence of severe infections was observed in patients that received plasmapheresis (p = 0.07)., Conclusion: Both plasmapheresis and conventional therapy improved eGFR at 12 months after intervention. Dialysis independence and survival were similar between groups. J. Clin. Apheresis 31:411-418, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA)., Methods: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons., Results: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil., Conclusion: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding., (© 2016, American College of Rheumatology.)

Background: The prevention of relapse and infection complications during remission maintenance therapy is required to improve the prognosis of patients with microscopic polyangiitis (MPA) showing rapidly progressive glomerulonephritis (RPGN). The clinicopathological characteristics of patients with ANCA-positive MPA were examined to determine the risk factors for relapse or infectious complications after remission induction therapy., Patients and Methods: The study population consisted of 52 patients diagnosed as ANCA-positive MPA showing RPGN from 2002 to 2012, after publication of the Japanese guideline for RPGN. The clinicopathological findings were examined between the presence and absence of relapse or infectious complications., Results: The value of vasculitis damage index (VDI) was high for the relapse group and VDI value was identified as the leading factor associated with relapse [hazard ratio (HR) 3.36, 95 % confidence interval (CI) 1.58-7.12, P < 0.01]. On the other hand, the values of Birmingham Vasculitis Activity Score, clinical grade category of RPGN at diagnosis, and VDI at remission were high in the infectious group. Furthermore, clinical grade category of RPGN was the leading factor associated with infectious complications (HR 5.30, 95 % CI 1.41-19.9, P = 0.01)., Conclusion: The disease activity at diagnosis and severity of organ damage at remission were associated with relapse and infectious complications during remission maintenance therapy and infectious complication affected kidney survival and all-cause mortality in patients with ANCA-positive MPA exhibiting RPGN.

Background: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis (AAV; ANCA denotes antineutrophil cytoplasmic antibody) that causes necrotizing inflammation of small blood vessels. Renal and pulmonary manifestations are common whereas central nervous system (CNS) involvement, and in particular spinal disease, is rare., Methods: We reviewed a case of MPA presenting with spinal intradural hemorrhage and intracerebral hemorrhage. We also summarized all reported cases of AAV with spinal cord involvement in the literature (database search included MEDLINE, Embase, Scopus, and Proquest with no date or language restriction)., Results: We reviewed 20 cases of AAV with spinal cord involvement (12 granulomatosis with polyangiitis [GPA], 4 eosinophilic granulomatosis with polyangiitis, 2 MPA, and 2 cases diagnosed as AAV only) and reported demographic information, clinical features, methods of diagnosis, treatment, and patient outcome. Although CNS involvement has been associated with a poor prognosis, 14 of 18 cases that reported outcome data achieved remission during follow-up. Death occurred in 3 patients diagnosed with GPA and in 1 patient with MPA. Our patient with MPA deteriorated rapidly despite use of prednisone and died., Conclusions: AAV can present with brain and spinal cord involvement, even in the absence of systemic disease. CNS disease may be responsive to immunosuppressive therapy (e.g., steroids and cyclophosphamide) in several of the cases reviewed., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Microscopic polyangiitis and granulomatosis with polyangiitis are rare anti-neutrophilic cytoplasmic antibody-associated systemic vasculitides that predominantly affect small to medium sized vessels of the lungs and kidneys. These syndromes are largely confined to older adults and often present sub-acutely following weeks to months of nonspecific prodromal symptoms. While both diseases often manifest within multiple organ systems concurrently, the disease spectrum of microscopic polyangiitis almost always includes the kidneys, while granulomatosis with polyangiitis is most commonly associated with pulmonary disease. We present two cases of rapid onset respiratory failure secondary to diffuse alveolar hemorrhage in young active duty military personnel. After serological testing and surgical lung biopsy, both patients were diagnosed with microscopic polyangiitis with isolated pulmonary involvement.

Objective: To describe the prevalence of major relapse and healthcare costs among patients with granulomatosis with polyangiitis (GPA); to find patients with microscopic polyangiitis (MPA) in administrative databases, because no MPA diagnosis code exists; and to describe the clinical and economic burden associated with MPA., Methods: Adults (≥ 18 yrs) with ≥ 2 diagnoses of GPA [International Classification of Diseases-9-Clinical Modification (ICD-9-CM 446.4)] during 2009-2013 were extracted from the Truven Health MarketScan Commercial and Medicare Supplemental databases. Evidence of major relapse (based on the Birmingham Vasculitis Activity Score) and healthcare costs were collected during 12-month and 24-month followup periods. Adults with ≥ 2 diagnoses of unspecified arteritis (ICD-9-CM 447.6) were found as potential patients with MPA and additional criteria based on clinical input were applied to refine the sample. Major relapse-associated conditions and healthcare costs in the 6 months pre- and post-diagnosis were measured. Costs were inflated to 2013 US$., Results: A total of 2784 patients with GPA were found and 18.7% experienced a major relapse in the 12-month followup period. The patients with a major relapse incurred higher average all-cause (12-month: $88,065 vs $30,682; p < 0.0001) and GPA-related costs (12-month: $61,636 vs $15,748; p < 0.0001) than patients without a relapse. Trends were consistent over the 24-month followup period. There were 612 incident patients with MPA. Following MPA diagnosis, healthcare costs nearly doubled ($30,166 vs $56,642; p < 0.0001)., Conclusion: In a real-world setting, patients with GPA who experience major relapse have higher economic burden, compared to patients without a relapse. MPA diagnosis was associated with nearly a 2-fold increase in healthcare costs.

The authors review the nomenclature of vasculitides and the classification of antineutrophil cytoplasm antibody associated vasculitides and present the method of measuring disease activity (Five-factor Score, Birmingham Vasculitis Activity Score) and its role in defining therapeutical needs. They discuss the treatment algorithm of antineutrophil cytoplasm antibody associated vasculitides, present the sometimes equipotential medications used during the induction therapy followed by a maintenance regimen, and outline their usage and possible side-effects that may require medical attention. They point out the importance of plasmapheresis as an adjunctive treatment in some cases, as well as indications and possible outcome of kidney transplantation in therapy-resistant cases. Finally, they review several ongoing clinical studies, as their outcome will probably influence therapeutical opportunities of antineutrophil cytoplasm antibody associated vasculitides in the next few years.

Background: This study describes the incidence and outcomes of European patients requiring renal replacement therapy (RRT) for kidney failure due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Study Design: Cohort study., Setting & Participants: 12 renal registries providing individual RRT patient data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry in 1993-2012 participated., Predictor: Cause of primary kidney disease: AAV (ie, granulomatosis with polyangiitis [Wegener] and microscopic polyangiitis) versus 3 separate matched control groups without AAV: (1) primary glomerulonephritis, (2) diabetes mellitus, and (3) disease other than diabetes mellitus as the cause of primary kidney disease, including glomerulonephritis (termed "nondiabetes")., Outcomes: Incidence, causes of death, and survival., Measurements: ERA-EDTA primary renal disease codes., Results: 2,511 patients with AAV (1,755, granulomatosis with polyangiitis; 756, microscopic polyangiitis) were identified, representing an incidence of 1.05 per million population (pmp) for granulomatosis with polyangiitis (predominating in Northern Europe) and 0.45 pmp for microscopic polyangiitis (prevailing in Southern Europe). Kidney transplantation was performed in 558 (22.2%) patients with vasculitis. The 10-year probability for survival on RRT after day 91 was 32.5% (95% CI, 29.9%-35.1%) in patients with vasculitis. Survival on RRT after day 91 did not differ between AAV and matched nondiabetes patients. Patient and transplant survival after kidney transplantation, adjusted for time period and country, was better in AAV than in matched nondiabetes patients (HRs of 0.81 [95% CI, 0.67-0.99] and 0.82 [95% CI, 0.69-0.96], respectively)., Limitations: No data for extrarenal manifestations, treatment, and relapses., Conclusions: Geographical differences in the incidence of RRT for kidney failure due to granulomatosis with polyangiitis and microscopic polyangiitis copied their distribution in the general population. Overall survival on RRT after day 91 for patients with AAV was similar to that for patients with nondiabetes diagnoses. Our results suggest that patients with AAV are suitable candidates for kidney transplantation with favorable survival outcomes., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical characteristics, laboratory features, outcome and prognosis of microscopic polyangiitis (MPA) patients with autoimmune hemolytic anemia (AIHA)., Methods: In this study, 63 cases diagnosed as MPA from October 2006 to November 2013 in Peking University People's Hospital were reviewed. The clinical characteristics, outcome and prognosis of MPA patients with AIHA were retrospectively analyzed., Results: There were 12.7% (8/63) MPA patients with AIHA. The patients with AIHA had higher prevalence of fever, fatigue, hematuresis, albuminuria and new-onset hypertension, compared with non-AIHA group(87.5% vs.29.1%;100% vs. 49.1%; 100% vs. 60%; 75% vs. 20%, all P<0.05). In patients with AIHA, there were significantly lower levels of red blood cell(RBC), hemoglobin(Hb), alanine albumin(Alb) and complement C3[(2.3±0.5)×10(12)/L vs.(3.0±0.7)×10(12)/L;(66.2±13.1) g/L vs.(90.0±20.3) g/L; (26.1±4.4) g/L vs. (33.5±6.4) g/L; (0.7±0.2) g/L vs.(0.9±0.3) g/L,all P<0.05]. However, the levels of erythrocyte sedimentation rate (ESR), IgG and Birmingham Vasculitis Activity Score (BVAS) were higher, compared with those in the patients without AIHA [(102.1±25.7) mm/1 h vs.(76.5±31.1) mm/1 h; (20.9±6.1) g/L vs. (14.5±6.0) g/L; ( 23.7±5.7) vs.(17.3±4.1), all P<0.05]. The study suggested that there were more severe multi-system damage in the patients with AIHA than in those without AIHA. In the MPA patients with AIHA, six cases received treatment of methylprednisolone combined with immunosuppressant, and two received treatment of methylprednisolone only. Among the eight cases, three were recovered from anemia and four improved. One died of severe lung infection. After 4 years follow-up,in the seven MPA patients with AIHA, three received remission, two died,and two suffered from anemia and abnormal renal function., Conclusion: MPA with AIHA is more complicated by multi-system damage and not rare in clinical settings. Glucocorticoid combined with immunosuppressant is beneficial to induce remission for MPA patients with AIHA.

Objective: To investigate the clinical features of patients with microscopic polyangiitis (MPA) and alveolar hemorrhage (AH), so as to raise the physicians' understanding of this condition., Methods: The clinical data of 15 MPA patients combined with AH, who were hospitalized in Peking Union Medical College Hospital from January 2008 to January 2014, were retrospectively analyzed., Results: These 15 subjects accounted for 18.1% of all MPA patients, including 4 males and 11 females with mean age of (59.4 ± 17.9) years old and mean disease duration of 7.5 (1-48) months. Hemoptysis or bloody sputum (14/15) and dyspnea (11/15) were predominant pulmonary manifestations. Hypoxemia appeared in 6 patients (40.0%). An average 8-46 (22.7 ± 4.4) g/L drop of hemoglobin level was seen in all 15 patients. Imaging revealed new bilateral infiltrations or opacities in 13 cases, and bloody bronchoalveolar lavage fluid were found in 6 cases. Compared with MPA patients without AH, the incidence of myalgia [2/15 vs 50.0%(34/68); P=0.009, OR=0.154] and hemoglobin level [(83.2 ± 21.0) g/L vs (102.5 ± 18.7) g/L; P=0.001] were statistically lower in MPA patients with AH. There were no statistical differences in age, sex, interstitial lung disease, renal involvement, peripheral neuropathy and the five factor score between two groups. The proportion of patients who received corticosteroid pulse treatment in MPA with AH group was significantly higher than that of MPA patients without AH [9/15 vs 19.1%(13/68); P=0.003, OR=6.346]. After treatment, 13 cases achieved remission, while 2 died., Conclusion: As an important pulmonary manifestation of MPA, AH could be insidious but fatal. The treatment with steroid, cyclophosphamide and plasma exchange could improve the prognosis.

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies.

Background: Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV)., Methods: We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed., Results: Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA., Conclusion: Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background/aims: Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We report the outcomes and safety profile of rituximab and glucocorticoid therapy for induction of remission in patients with AAV and ANCA-negative vasculitis presenting with severe renal disease., Methods: A multicenter, retrospective, cohort study was conducted between 2005 and 2014. Patients with new or relapsing disease with an estimated glomerular filtration rate (eGFR) of ≤20 ml/min/1.73 m(2) treated with rituximab and glucocorticoid induction with or without plasmapheresis were included. Fourteen patients met the inclusion criteria. The primary outcomes were rate of remission and dialysis independence at 6 months. The secondary outcomes were eGFR at 6 months, end-stage renal disease (ESRD), survival rates and adverse events., Results: All patients were Caucasian, and 57% were male. The mean eGFR was 12 ml/min/1.73 m(2) at diagnosis. All patients achieved remission with a median time to remission of 55 days. Seven patients required dialysis at presentation of which 5 patients recovered renal function and discontinued dialysis by 6-month follow-up. The mean eGFR for the 11 patients without ESRD who completed 6-month follow-up was 33 ml/min/1.73 m(2). Four patients ultimately developed ESRD, and one died during the follow-up period., Conclusion: Patients with AAV and severe renal disease achieve high rates of remission and dialysis independence when treated with rituximab and glucocorticoids without cyclophosphamide., (© 2015 S. Karger AG, Basel.)

The aim of our study was to analyze clinical features, laboratory findings, treatment, course and outcome of different types of vasculitis in children. All children aged up to 18 years that have been diagnosed with a vasculitis disorder from 2002. to 2012. at the Department of Paediatric, University Hospital Centre Zagreb according to EULAR/PRES/PRINTO criteria were included in the study. Vasculitis was diagnosed in 180 children, 101 girls and 79 boys, mean age 7.19 ± 3.7 years, with an average follow-up of 5.58 ± 3.28 years. Most of the children (155 or 86%) were diagnosed with Henoch-Shönlein purpura (HSP), polyarteritis nodosa (PAN) was diagnosed in 6 children (3.3%), isolated cutaneous leukocytoclastic vasculitis in 5 (2.8%), Takayasu arteritis (TA) and Kawasaki disease in 2 (1.1%) respectively, hypocomplementemic urticarial vasculitis in one patient (0.5%) and other types of vasculitis in 10 (5.5%) patients (vasculitides in systemic connective tissue disorders in 7 and unclassified vasculitides in 3 patients). All patients had elevated inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Anti-neutrophil cytoplasmatic antibodies (ANCA) were positive only in one patient, suffering from microscopic polyangiitis. Treatment modality in most patients were NSAIDs, while children with kidney or gastrointestinal system affection were treated with glucocorticoids and/or immunosuppresive drugs. Biological therapy (anti-CD20, rituximab) was used in patients with most severe symptoms. One child (0.56%), suffering from microscopic polyangiitis, died due to kidney failure during the follow-up. Forty patients (22.6%) had one disease relapse, while 6 (3.4%) had two relapses. In conclusion, we found some differences in laboratory parameters (e.g. lower incidence of elevated antistreptolysin O titer in HSP) and epidemiological data (e.g. higher prevalence of PAN in female children) in comparison to data from available studies, while other clinical features, laboratory findings, disease outcome and treatment were similar.

Background: The aim of this study was to identify risk factors for end-stage renal failure (ESRF) or death in Japanese patients with microscopic polyangiitis (MPA) with renal involvement., Methods: From 54 consecutive patients with systemic vasculitis based on Watt's algorithm, we retrospectively analyzed 39 MPA patients with renal involvement, including 19 (48.7 %) with renal-limited vasculitis., Results: Thirty-three of 39 patients (84.6 %) demonstrated rapidly progressive glomerulonephritis, and 13 (33.3 %) developed ESRF; 8 of 13 required dialysis within 1 week. Thirteen (33.3 %) died during follow-up of more than 12 months, and 7 died during the first 6 months, mainly because of opportunistic infections. Overall survival at 6 and 12 months was 79.5 and 71.1 %, respectively. Serum creatinine levels did not differ significantly between survivors and non-survivors (P = 0.092). The mean Birmingham Vasculitis Activity Score, version 3 (BVAS v.3), was 16.2 ± 6.5, with a renal subscore of over 12 points in 82.1 %, and BVAS v.3 was marginally higher in non-survivors than survivors (P = 0.045). An age- and sex-adjusted Cox proportional hazards analysis demonstrated that neither the serum creatinine level (P = 0.277) nor BVAS v.3 (P = 0.188) at initial diagnosis was a risk factor for overall survival. The baseline serum creatinine cutoff value for discriminating between ESRF and non-ESRF was 4.6 mg/dl, with a sensitivity and specificity of 92.3 and 84.6 %, respectively., Conclusions: Survival rates do not relate to ESRF in MPA patients with mainly renal involvement. Although patients with ESRF required regular hemodialysis, longer survival can be achieved.

Introduction: Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature., Methods: All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified., Results: Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed., Conclusions: Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Aim: Gastrointestinal (GI) involvement in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) is rare., Method: Medical charts of seven patients with GPA and MPA and GI involvement were reviewed regarding clinical presentation, outcome, diagnostic tools and therapy. Second, the cellular composition of the inflammatory infiltrate associated with the vascular lesions in histological samples (ileum, colon, rectum, duodenum) were investigated to identify possible treatment targets. Immunohistochemistry was done with antibodies against CD20, CD3 and CD34. Samples from a healthy control group (n = 15) were used for comparison., Results: Mean age at onset of the first symptoms of vasculitis was 48 ± 21.3 years. At time of diagnosis GI symptoms were present in five out of seven patients (71%) and occurred during relapse of the vasculitis in two patients (29%). All patients had abdominal pain, four of seven (57%) had an acute kidney injury and three patients required renal replacement therapy. At the time of diagnosis five of seven patients (71%) required surgery and mean Birmingham Vasculitis Activity Score (BVAS) on admission was high (26.3 ± 7.7). Regarding outcome, one patient died due to gastrointestinal bleeding. Histological analysis showed significantly higher expression of CD3 in this patient compared to the control group (P = 0.02). Analysis of expression of CD20 and CD34 showed no statistically significant differences between patients with GPA and MPA with GI involvement compared to the control group., Conclusions: GI involvement in GPA and MPA is rare. Therapy directed at T cells might be an alternative treatment option., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Microscopic polyangiitis (MPA) is a systemic autoimmune disease that often has a fatal outcome. Although delineating the molecular pathogenesis is essential for its remedy, an understanding of its molecular mechanism has remained elusive. To search for new markers of active lesions that might help better understand the molecular basis of MPA and aid in its diagnosis, we here performed DNA microarray analysis with peripheral blood mononuclear cells (PBMCs). Compared to normal control, several genes were up- or down-regulated in MPA patients, including up-regulation of the mRNA level of ficolin-1 (FCN1 or M-ficolin), an innate pattern recognition complement molecule. The amount of ficolin-1, as detected by immunohistochemistry, was higher in the glomeruli of another group of MPA patients than in the glomeruli of control patients who harbored almost normal glomeruli. Many of the ficolin-1 dots were also positive for CD68, suggesting that the ficolin-1-positive cells were monocytes, such as macrophages or dendritic cells. This is not due to the difference in the number of neutrophil or monocytes in the blood samples of MPA and control patients. Taken together, we conclude that increased ficolin-1 expression could serve as a new marker for the characterization of MPA, especially when it is associated with local active lesions.

Microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and Wegener's granulomatosis are anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides that may affect both the central and peripheral nervous systems. In these diseases, the frequency of concomitant peripheral neuropathy is particularly high in MPA and CSS. As opposed to kidney and lung involvement, which may be life threatening, peripheral neuropathy due to vasculitis alone does not significantly affect survival, although it can disturb day-to-day functioning and quality of life of patients. In this article, we describe clinical and pathological features of neuropathy in ANCA-associated vasculitides, focusing on MPA and CSS. A mononeuritis multiplex pattern instead of a symmetric polyneuropathy pattern characterizes the neuropathic features of MPA and CSS. Pathological findings of vasculitic neuropathy are characterized by axonal degeneration of nerve fibers caused by vasculitis-induced ischemia in both MPA and CSS. Hence, CSS- and MPA-associated neuropathies share common neuropathic features, but the extent of systemic organ involvement is significantly higher in MPA cases, resulting in poorer survival rates.

The diagnosis and treatment of granulomatous lung diseases is challenging. This article describes two of these entities: (1) eosinophilic vasculitis with polyangiitis which is clinically characterized as a combination of bronchial asthma and eosinophilic granulomatous vasculitis. Antoneutrophil cytoplasmic antibodies are present in approximately 40 % of patients. Treatment with steroids is sufficient in patients with isolated pulmonary manifestation but extrapulmonary manifestations, e.g. heart, central nervous system (CNS), kidneys and gastrointestinal tract warrant combined immunosuppression with prednisolone and cyclophosphamide. (2) In Germany tuberculosis is an orphan disease with an incidence of 5.3/100,000 in the year 2011. Prolonged cough, night sweats and weight loss should be considered suspicious of tuberculosis. Microbiological diagnosis has been improved by gene and PCR technology. The traditional Mendel-Mantoux skin test has widely been replaced by the interferon gamma release assay (IGRA). Standard treatment of non-resistant mycobacterium tuberculosis is based on a combination of isonizide, rifampicine, pyrazinamide and ethambutol for 2 months followed by 4 months of isoniazide plus rifampicine. Therapy resistant, multiple drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis bacteria should be treated by experienced specialists.

Background: This study aimed to describe the epidemiologic characteristics of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan., Methods: We used the database of the Ministry of Health, Labour and Welfare (MHLW) from 2006 to 2008, and analyzed data from 938 patients (MPA = 697, GPA = 241) who fulfilled the MHLW diagnostic criteria and had registered within a year after onset., Results: The mean ages of the MPA and GPA patients were 69.4 ± 0.4 and 58.4 ± 1.1 years, respectively. Renal (86.9 %), chest (73.7 %), and nervous system (45.2 %) symptoms were common in MPA patients. Ear, nose, and throat (86.7 %), chest (78.0 %), and renal (60.6 %) symptoms were frequently observed in GPA patients. The concomitant use of cyclophosphamide (CY) with corticosteroids was observed in 22.2 % of the MPA patients and 58.5 % of the GPA patients. In multivariate analysis, the concomitant use of CY was associated with a younger age and pulmonary hemorrhage in MPA patients, and the avoidance of CY was associated with nervous system symptoms and rapidly progressive glomerulonephritis in GPA patients. Plasma exchanges were inducted in 5.2 % of the MPA patients and 4.1 % of the GPA patients. The addition of plasma exchange was associated with elevation of the serum creatinine level in patients with both MPA and GPA., Conclusion: A dominance of MPA and a reduced frequency of renal involvement in GPA patients may be significant features of the Japanese population. Clinical practice relating to MPA and GPA in Japan can be characterized as follows: CY is used less commonly, and plasma exchange is employed for patients with deteriorated renal function.

The pulmonary vasculitides are a heterogeneous group of disorders characterized pathologically by vascular destruction with cellular inflammation and necrosis. These disorders can affect small, medium, and large vessels and may be primary or occur secondary to a variety of conditions. Vasculitis involving the lungs is most commonly due to primary, idiopathic, small-vessel antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, which includes granulomatosis with polyangiitis (formerly Wegener's granulomatosis), Churg-Strauss syndrome, and microscopic polyangiitis. From a clinical perspective these remain among the most challenging of diseases both in terms of diagnosis and treatment. This review will focus on diagnosis and management of ANCA-associated vasculitides.