The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

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.

Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

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.

Incidence of anti-neutrophil cytoplasmic antibody-associated renal vasculitis: a retrospective study in rural and regional Victoria, Australia.

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.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

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.

[Diagnosis and therapy of granulomatosis with polyangiitis and microscopic polyangiitis-2023: consensus of the Austrian society of nephrology (ÖGN) and Austrian society of rheumatology (ÖGR)]. / Diagnose und Therapie der Granulomatose mit Polyangiitis und mikroskopische Polyangiitis ­ 2023: Konsens-Empfehlungen der Österreichischen Gesellschaften für Nephrologie (ÖGN) & Rheumatologie (ÖGR).

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).

Monitoring disease activity in antineutrophil antibody-associated vasculitis.

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.

Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations.

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.

Stable incidence but increase in prevalence of ANCA-associated vasculitis in southern Sweden: a 23-year study.

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.

Clinical Characteristics and Outcomes of Patients With ANCA-Associated Vasculitides in a Colombian Hospital.

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.

[Pediatric ANCA-associated vasculitis, a case series]. / Vasculitis asociadas a ANCA en pediatría, serie de casos clínicos.

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.

Updates in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis: At a crossroad.

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.

Lung involvement in ANCA-associated vasculitis.

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.

ANCA-Associated Vasculitis: Core Curriculum 2020.

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.

Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis.

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.

Pulmonary vasculitis: diagnosis and treatment.

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.

Severe microscopic polyangiitis with unilateral vocal cord paralysis as initial manifestation.

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.

DESCRIPCIÓN DEL CASO: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. HALLAZGOS CLÍNICOS: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. TRATAMIENTO Y DESENLACE: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. RELEVANCIA CLÍNICA: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.

Clinical and prognostic features of Korean patients with MPO-ANCA, PR3-ANCA and ANCA-negative vasculitis.

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.

Severe microscopic polyangiitis with unilateral vocal cord paralysis as initial manifestation / Parálisis unilateral de cuerda vocal como manifestación inicial de poliangitis microscópica grave

Abstract 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.

Resumen Descripción del caso: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. Hallazgos clínicos: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. Tratamiento y desenlace: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. Relevancia clínica: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

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.

Microscopic Polyangiitis with Spinal Cord Involvement: A Case Report and Review of the Literature.

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.