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.

Proteinase 3-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.

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.

Diagnosis and management of facial nerve palsy secondary to granulomatosis with polyangiitis - A systematic review.

OBJECTIVE: Granulomatosis with polyangiitis is associated with otolaryngologic complaints in 70-95 % of cases, with the most common being serous otitis media. In rare cases, patients may experience facial nerve palsy in conjunction with otologic or nasal symptoms; and, often, initially present to an otolaryngologist. It is important for healthcare professionals to be able to recognize the nuisances of facial nerve palsy as a potential presentation of granulomatosis with polyangiitis. STUDY DESIGN: Systematic review. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocol, PubMed and MED-LINE Databases were queried for articles published from January 2007 to December 2022 describing facial nerve palsy in the context of Granulomatosis with polyangiitis, formerly known as Wegener's Granulomatosis. The keywords included "facial nerve palsy", "facial palsy", "granulomatosis with polyangiitis", "Wegener's granulomatosis", "ANCA positive" in the title/abstract. All full-text articles available in English were screened, including single case presentations. Abstracts, commentaries, and publications deemed outside the scope of our study aims were excluded from review. After removal of duplicate articles, a total of 85 articles were screened. After applying inclusion and exclusion criteria, 14 articles were included in the review. RESULTS: There were a total of 28 reports of facial nerve palsy in the literature in patients who were eventually diagnosed with granulomatosis with polyangiitis. The patients' ages ranged from 14 to 68 years old. None of the patients had been previously diagnosed with GPA, and a majority of them presented initially with other otologic symptoms. Hearing loss was reported in 24 patients (86 %), otalgia was present in 11 patients (39 %), and otorrhea was present in 6 patients (21 %). Bilateral facial paralysis was reported in 10 patients in the literature (36 %). In total, 16 patients underwent surgery for facial paralysis: 6 tympanomastoidectomies, 4 mastoidectomies, 2 explorative tympanotomies. Surgery was generally considered ineffective in resolving facial weakness. All patients ended up receiving some combination of steroids and immunosuppressant, most commonly prednisolone and cyclophosphamide or rituximab, which was eventually transitioned to azathioprine for maintenance. Unlike auditory thresholds, which remained decreased in two patients, all patients recovered facial function following appropriate medical treatment of their vasculitis. CONCLUSIONS: Facial nerve paralysis in patients with granulomatosis with polyangiitis is a rare but treatable phenomenon. In patients with intractable otitis media, unresolving facial palsy, or a combination of otologic issues, it is important to consider GPA as a possible source. The prognosis for facial function appears to be excellent in patients who undergo appropriate treatment for vasculitis, but further studies are needed for confirmation.

[Vasculitides]. / Vaskulitiden.

In everyday clinical practice, immunologically mediated systemic vasculitides are among the rare diseases, meaning that basic knowledge of major symptoms and indicative laboratory findings is crucial for the inclusion of these complex clinical entities in differential diagnostic considerations. For many years, systemic vasculitides have been classified according to the primarily affected vessel size, distinguishing large, medium-sized, and small vessels. Pain is very often one of the main complaints of these diseases, be it, for example, the temporally accentuated headache in giant cell arteritis, the early morning myalgias in the shoulder and hip girdle in polymyalgia rheumatica, or the mononeuritis multiplex in eosinophilic granulomatosis with polyangiitis. General symptoms such as fever, weight loss, and night sweats are often accompanied by greatly increased parameters of inflammation. In addition, organ-specific symptoms and/or laboratory abnormalities may provide crucial information. These include ENT symptoms, pulmonary or skin manifestations, as well as signs of renal involvement, such as peripheral edema, rise in blood pressure, hematuria, proteinuria, or a rapid loss of kidney function. If there is reasonable suspicion of disease, patients should be transferred to specialized centers with an interdisciplinary team. In most cases, an immunosuppressive therapy regimen is required, although in recent years the path towards avoiding high glucocorticoid doses with many side effects has been paved by the use of novel therapies.

Eosinophilic Granulomatosis With Polyangiitis Following COVID-19 Vaccination: A Case Report.

The current emergence of the coronavirus disease 2019 (COVID-19) pandemic and the possible side effects of COVID-19 mRNA vaccination remain worrisome. Few cases of vaccination-related side effects, such as vasculitis, have been reported. Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a type of vasculitis characterized by the histological richness of eosinophils, asthma, polyneuropathy, sinusitis, and skin or lung involvement. Here, we report the first case of new onset EGPA following COVID-19 vaccination in Korea. A 71-year old woman developed a skin rash and presented with progressive weakness of the upper and lower extremities after the BNT162b2 vaccination (Pfizer-BioNTech). She was diagnosed with EGPA and her symptoms improved after systemic steroid and immunosuppressant therapy. Although it is very rare, clinicians should be aware that EGPA may occur after COVID-19 vaccination.

[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).

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.

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.

[Eosinophilia: hypereosinophilic syndrome vs. eosinophilic granulomatosis with polyangiitis]. / Eosinophilie: hypereosinophiles Syndrom versus eosinophile Granulomatose mit Polyangiitis.

Hypereosinophilic syndrome (HES) is defined as a peripheral eosinophil count of > 1500/µl (assessed twice at an interval of ≥ 2 weeks) and an eosinophil-induced organ damage. Idiopathic HES is differentiated from primary (clonal or neoplastic) HES and secondary (reactive) HES, depending on the etiology. Eosinophilic granulomatosis with polyangiitis (EGPA) is categorized as a secondary form of HES and is characterized by hypereosinophilia and vasculitis of small to medium-sized vessels and can be associated with an antineutrophil cytoplasmic antibody (ANCA). The treatment of HES is dependent on the etiology. Clonal HES is treated according to the respective genetic aberration, e.g. with tyrosine kinase inhibitors or chemotherapy and allogenic stem cell transplantation. Secondary forms should be treated according to the underlying cause (e.g. parasitic infection). The treatment of EGPA is carried out with immunosuppressants depending on the disease stage and disease activity. Conventional drugs, such as glucocorticoids (GC), cyclophosphamide (CYC) and methotrexate (MTX) or biologics, such as the monoclonal anti-IL5 antibody mepolizumab are commonly used. Mepolizumab is also a good option for the treatment of idiopathic HES.

[Granulomatosis with polyangiitis: what's new?] / Granulomatose avec polyangéite : quoi de neuf ?

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.

La granulomatose avec polyangéite (GPA) fait partie des vasculites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA). La maladie touche principalement la sphère ORL, les poumons et les reins. Son incidence est de 10 à 20 cas/million/année. Les ANCA sont pathogéniques en induisant une activation des polynucléaires neutrophiles, entraînant des lésions endothéliales. Le diagnostic est facilité par la détection des ANCA, qui peuvent cependant être absents dans les formes ORL limitées. La prise en charge est multidisciplinaire. Le traitement comprend une phase d'induction et une autre de maintien de la rémission, associant corticostéroïdes et immunosuppresseurs. L'objectif du traitement est de limiter le risque important de rechute et de réduire la toxicité des corticostéroïdes.

Unmet needs and evidence gaps in hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes.

A rare case of granulomatosis with polyangiitis with involvement of the gastrointestinal system.

We report a rare case of a 37-year-old man with granulomatosis with polyangiitis (GPA) with gastrointestinal system (GIS) involvement who needed 526 units of blood and blood product transfusions and was followed up in the intensive care unit (ICU). GIS involvement due to GPA is a rare condition that increases morbidity and mortality of patients. Patients may require ultramassive blood product transfusions. Thus, patients with GPA can be admitted to ICUs because of massive hemorrhage due to multisystem involvement, and survival is achievable with meticulous care through a multidisciplinary approach.

Oral manifestations of anti-neutrophil cytoplasmic antibody-associated vasculitis: an update and narrative review of the literature.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a multisystem disorder of small blood vessels subdivided into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Oral manifestations (OMs) have been reported to include mucosal ulceration, gingival enlargement, alveolar bone necrosis, tooth loss, oro-antral communication, palatal perforation, parotitis, and candidal infection mainly in GPA. They may appear during the course of the disease, as a disease flare-up, or as the presenting sign. These OMs are often nonspecific and can mimic an array of conditions, therefore formulating a differential diagnosis can be challenging. This review updates the OMs of GPA, and, for the first, time includes OMs of other AAVs. It provides recommendations for the overall assessment and the diagnosis and management of all AAV OMs with considerations for treatment coordination. The role of oral health care providers in multidisciplinary care is highlighted.

Oral granulomatosis with polyangiitis a systematic review.

OBJECTIVE: Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for upper lower airways and kidneys. The etiology remains unknown although it may originate from different stimuli, in genetically susceptible patients. MATERIALS AND METHODS: A detailed database search was performed. The variables were demographics, localization, histopathological findings, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA) tests, treatment, and follow-up. RESULTS: Fifty-two cases were identified; the mean age was 49.6 years, with a range from 6 to 87 years. It was most frequently seen in females (57.7%). The most common race was white (59.6%). The most frequent location was in the maxillary gingiva (28.8%), followed by both the upper and lower gingiva (19.2%). The most common clinical presentation was "strawberry gingivitis" (61.5%). The main symptom was pain, in 50%. Regarding the c-ANCA test, it was positive in 71.2% of cases. The most common therapy was prednisone and cyclophosphamide, utilized in 51.9%. The average follow-up was 23.6 months, and 88.5% of patients were still alive at follow-up. CONCLUSION: The diagnosis initially was difficult to establish, an early diagnosis and treatment are mandatory. If untreated the disease can be associated with morbidity and mortality. For the oral clinician, this disease needs to be addressed in the differential diagnosis of oral lesions.

Clinical profile and management of granulomatosis with polyangiitis-associated scleritis from a tertiary care hospital in South India.

Purpose: To describe the clinical features and management of patients with scleritis associated with granulomatosis with polyangiitis (GPA) at a tertiary eye care center in South India. Methods: The clinical profile and management of patients presenting to a tertiary eye care center in South India with scleritis secondary to GPA from 2003 to 2021 were analyzed retrospectively. Scleritis was classified into anterior diffuse, nodular, and necrotizing scleritis with inflammation according to Watson and Hayreh's classification. Demographic characteristics, clinical features, anti-neutrophil cytoplasmic antibody (ANCA) positivity, treatment response, ocular complications, and status at the last follow-up were analyzed. Statistical analysis of data was performed using Microsoft Excel 2019. Results: Nineteen eyes of 17 patients (15 cytoplasmic staining ANCA [c-ANCA], two p-ANCA positive) were included. Fifteen eyes had necrotizing scleritis, two had diffuse anterior scleritis, and two had nodular scleritis. Remission was induced using a combination of steroids and cyclophosphamide or rituximab. Maintenance therapy was instituted using tapering steroids and immunosuppressants like cyclophosphamide, mycophenolate mofetil, methotrexate, or rituximab. Three eyes required a scleral patch graft. Fourteen patients had good anatomical and visual outcomes, and three were lost to follow-up. Conclusion: GPA is a rare disease, while it is the most common ANCA-associated vasculitis with scleritis. As scleritis may be the presenting sign of the disease, ophthalmologists must be aware of the various features suggestive of GPA. GPA-associated scleritis can have a good prognosis when diagnosed promptly and managed aggressively in the acute stage, and remission is maintained with adequate systemic immunosuppression.

Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis.

BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.