ANCA-positive Vasculitis Research Articles

Pyoderma Gangrenosum-like Ulcers Associated Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis is an ANCA-positive vasculitis primarily affectingsmall to medium-sized vessels, typically involving the lungs and kidneys. This articlepresents a remarkable case of a patient with an unusual pyoderma gangrenosum-likeulcer on the face and granulomatosis with polyangiitis. A 28-year-old man, previouslydiagnosed with granulomatosis with polyangiitis, presented at a dermatology clinic with a 6-month-old ulcer in the right preauricular region following a traumatic incident. A spindle biopsy revealed suppurative granulomatous dermatitis with secondary vascular damage, while cultures showed no signs of infection. The patient was subsequently treated with rituximab, leading to a positive clinical response. This case underscores the challenge of diagnosing this rare manifestation of granulomatosis with polyangiitis and suggests that rituximab could be a valuable treatment option.

Microscopic polyangiitis, an onset with diffuse alveolar hemorrhage

Introduction: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of complex chronic diseases that cause morbidity, systemic organ damage, therapeutic overload, and risk of relapse. Microscopic polyangiitis (MPA) primarily affects small vessels in the lungs and kidneys, characterized by inflammation that can lead to necrosis of blood vessels, presence of ANCA in the bloodstream, and absence of necrotizing inflammation of the parenchyma in histopathology. Methods: we present the case of a 58-year-old female patient with hemoptysis, fever, and dyspnea. Results: laboratory tests show anemia, leukocytosis, positive p-ANCA, hematuria, and proteinuria. The CT scan reveals areas of increased attenuation with a ground-glass pattern and centrilobular nodular opacities occupying the middle lobe and both lower lobes. The patient also tested positive for MPO-ANCA, leading to the diagnosis of ANCA-positive vasculitis, specifically microscopic polyangiitis with pulmonary and renal involvement, pneumonia, and renal insufficiency. She received appropriate medical treatment, resulting in adequate resolution. Conclusions: microscopic polyangiitis requires interdisciplinary management, which, along with radiological findings, contributes to the early diagnosis and timely treatment of the pathology

A case of renal limited myeloperoxidase anti-neutrophil cytoplasmic antibody-positive vasculitis treated with maintenance avacopan monotherapy.

A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333IU/mL), proteinuria (1.21g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.

ANCA-Positive Small-Vessel Vasculitis Following SARS-CoV-2 Vaccination-A Systematic Review.

As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients' metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination.

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first β-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30days (n = 358, 55.68%). However, AEs were still possible after 1year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

Propylthiouracil-induced ANCA-positive vasculitis in Graves’ disease

Implication for health policy/practice/research/medical education: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is an infrequent autoimmune disease that involves small vessels. Vasculitis triggers include infections, drugs, and chemicals. Propylthiouracil (PTU) is the most reported drug implicated in the induction of ANCA-associated vasculitis. The involvement of hematological systems, skin, gastrointestinal systems, kidneys, musculoskeletal systems, lungs, and neurological systems are seen in PTU-induced vasculitis. The exact pathogenesis of ANCA induction and PTU-induced vasculitis is not fully understood. Diagnosing PTU-induced ANCA-positive vasculitis involves a combination of clinical, laboratory, imaging, and histopathological findings.

Propylthiouracil induced ANCA-positive vasculitis in a patient with Graves’ disease; a case report

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is rare, but it can be triggered by chemicals, infections, and drugs. Patients who use anti-thyroid drugs are prone to involve with ANCA-associated vasculitis. Perinuclear ANCA (p-ANCA) is almost always positive in these patients. Patients have various presentations and symptoms such as (arthritis, edema) and this disorder usually resolves with discontinuation of the drug, however, some patients require high-dose steroids, immunosuppressive or plasmapheresis. A 38-year-old woman with a history of Graves’ disease was on long-term treatment with propylthiouracil (PTU), presented with severe bone pain, arthritis and edema in both feet. The patient’s manifestations were resolved with discontinuation of PTU, iodine therapy, and corticosteroid administration.

E021 A rare case of coexistence of ANCA-associated vasculitis and malignancy

Abstract Background/Aims A 65-year-old man, with a background of COPD, peripheral vascular disease and a neurostimulator in situ for chronic back pain, presented with a range of symptoms initially treated as lower respiratory tract infection in the community. He complained of bitemporal headache, jaw-pain, transient visual loss and had raised inflammatory markers (CRP 157 and ESR 105). He was subsequently treated as giant cell arteritis with 60mg prednisolone daily despite equivocal temporal artery ultrasound. He continued to have drenching sweats, arthralgia, epistaxis, shortness of breath and haemoptysis although inflammatory markers had normalised. Immunology revealed a strongly positive anti-PR3 antibody at > 8 units suggestive of granulomatosis polyangiitis. There was no convincing end organ evidence of vasculitis. CT-chest identified nodules and non-specific inflammatory changes but no cavitation or pulmonary haemorrhage. He was intolerant of steroids with significant insomnia and mood changes therefore they were rapidly tapered to 20mg daily. Methods He was readmitted to hospital on 20mg prednisolone with acute abdominal pain. CT abdomen-pelvis showed a lesion at the hepatic flexure suspicious for colon cancer, and this was confirmed on colonoscopy and biopsy. PET-CT at this time showed no evidence for active large vessel vasculitis. His prednisolone was tapered further and omitted prior to right hemicolectomy. Histology revealed definitive adenocarcinoma along with a focus of necrotising vasculitis and granulomas in the subserosa close to the tumour, with a distant granulomatous lesion at the resected appendix. He developed post-operative ileus and desaturated leading to a CTPA which did not show PE but identified progressive enlargement of the pulmonary nodules reported as suspicious of metastases. Throughout this time PR3 remained elevated and repeat PET-CT off steroids showed increased uptake at the aorta and right common iliac artery suggestive of active vasculitis. The FDG uptake and rate of enlargement of the pulmonary nodules was felt to be out of keeping with metastases and an inflammatory cause was suspected. Results Episodic pyrexia continued with no identifiable infective source and so a decision to commence oral prednisolone 40 mg was made. Repeat PET-CT 4 weeks later showed complete resolution of the inflammation in the aorta and right common iliac and reduction in size of the lung nodules. Unfortunately, the patient developed acute pancreatitis on steroids, so the prednisolone was reduced to 20mg with a view to induction therapy with cyclophosphamide. Conclusion This case highlighted multiple diagnostic challenges with clinical features of large vessel involvement in a patient with a positive ANCA and concomitant occult malignancy. Co-existence of a vasculitis and a neoplastic disease is rare. ANCA positive vasculitis is most commonly reported with haematological malignancies but less so in solid tumours, presenting as a paraneoplastic phenomenon. This case also highlighted the challenges in management when both conditions co-exist. Disclosure S. Ahmed: None. E. Pathan: None. P. Brown: None. J. Heaney: None. A. Pratt: None.

ANCA-associated hypertrophic pachymeningitis, a central nervous system limited type of systemic vasculitis.

LEARNING POINT FOR CLINICIANS Hypertrophic pachymeningitis (HP) is characterized by a thickening of the dura mater that in some cases has been related to systemic diseases. Some hearing loss may be the first clinical manifestation of PH as a form of ANCA-positive vasculitis limited to the brain. Treatment with rituximab appears to be a good therapeutic option for these cases.

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

Herpes Zoster Precipitating First Attack of Neuromyelitis Optica along with Perinuclear Anti-Neutrophilic Cytoplasmic Antibody Positive Vasculitis.

Herpes Zoster Precipitating First Attack of Neuromyelitis Optica along with Perinuclear Anti-Neutrophilic Cytoplasmic Antibody Positive Vasculitis.

Compromiso gastrointestinal inusual en paciente pediátrico con vasculitis asociada a anticuerpos anticitoplasma de neutrófilos. Reporte de un caso

Vasculitis is characterized by presenting inflammation of the wall of blood vessels, one type of these diseases are those associated with anti-neutrophil cytoplasm antibodies. They usually occur in adulthood and are rare in childhood. The disease generally affects the lung, kidney, and skin, with gastrointestinal involvement being rare. Here we describe the case of a pediatric patient with gastrointestinal bleeding secondary to ANCA positive vasculitis. Endoscopy revealed patchy erythematous lesions and wall hematoma at the level of the colon. Although we report a fairly infrequent clinical condition, it is not without complications. We believe it is appropriate to suspect it, first of all, intestinal involvement where the underlying inflammatory process is not clear, even more so when it involves other organs.

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Clinical features and outcomes of elderly patients with antineutrophil cytoplasmic antibody-positive vasculitis: a single-center retrospective study.

BackgroundWe aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea.MethodsSeventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged <65 years) or elderly (aged ≥65 years) groups. Initial induction treatments were investigated according to age group. All-cause mortality and kidney outcomes were evaluated.ResultsAfter categorization by age, 34 (48.6%) and 36 patients (51.4%) were in the younger and elderly groups, respectively. In the elderly group, more patients were treated with oral cyclophosphamide (CYC) (30.6%) than with intravenous CYC (19.4%). During a median follow-up of 14.6 months (range, 3.0–53.1 months), 13 patients died (elderly group: 11 patients, 84.6%). In the elderly group, older age (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09–1.90; p = 0.01), lower hemoglobin (HR, 0.21; 95% CI, 0.08–0.60; p = 0.003), and higher serum creatinine level (HR 14.17; 95% CI, 1.29–155.84; p = 0.03) were significant risk factors for all-cause mortality after adjustment. Oral CYC + steroid treatment was associated with decreased all-cause mortality compared to untreated induction immunosuppressants (HR, 0.01; 95% CI, 0.001–0.47; p = 0.02). Kidney failure or kidney recovery outcomes were not significantly different between the younger and elderly groups.ConclusionPatients aged ≥65 years had higher mortality rates than younger patients, and mortality was associated with older age, lower hemoglobin, higher serum creatinine level, and nontreatment compared to oral CYC + steroids.

A Worldwide Pharmacoepidemiologic Update on Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Era of Targeted Therapies.

The literature supporting the role of a specific drug in the onset of drug-induced antineutrophil cytoplasmic antibody-associated vasculitis (AAV) mainly relies on case reports or short series and implicates old treatments. The advent of new treatments may have modified the epidemiology of these adverse drug reactions. This study was undertaken to update the list of drugs associated with AAV by using a pharmacovigilance-based data mining approach. We collected data on adverse drug reactions reported using the Medical Dictionary for Regulatory Activities preferred term "anti-neutrophil cytoplasmic antibody positive vasculitis" up to November 2020 from the World Health Organization pharmacovigilance database (VigiBase). For each retrieved drug, a case-noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC025 value, which is the lower end of the 95% credibility interval, was considered significant. A total of 483 deduplicated individual case safety reports of drug-induced AAV involving 15 drugs with an IC025 >0 were retrieved. Of the individuals with drug-induced AAV for whom data on sex were available (n = 371), 264 (71.2%) were women. The median age at onset of drug-induced AAV was 62 years (quartile 1 [Q1]-Q3 45-72 years), and the median time from the introduction of the suspected drug to the onset of drug-induced AAV was 9 months (Q1-Q3 1-36 months). Drug-induced AAV was considered serious in 472 (98.1%), and was fatal in 43 (8.9%), of 481 cases. The drugs associated with the highest disproportionate reporting were hydralazine, propylthiouracil, thiamazole, sofosbuvir, minocycline, carbimazole, mirabegron, and nintedanib. Our findings strengthen the evidence of an association of AAV with previously suspected drugs, but also identify 3 new drugs that may cause drug-induced AAV. Particular attention should be given to these drugs by prescribers and in experimental studies.

27395 ANCA-positive hemorrhagic vasculitis with severe myositis—Atypical presentation of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Patient history: A 41-year-old female with a past medical history of asthma presented to the emergency department for diffuse myalgias and a cutaneous eruption gradually worsening over two weeks. Physical examination showed symmetric violaceous papules and nodules on the dorsal arms and hemorrhagic vesicles overlying palpable purpura on the lower extremities. During admission she developed profound dysphagia and severe systemic muscle weakness.

POS0118 A WORLDWIDE PHARMACOEPIDEMIOLOGICAL UPDATE OF DRUG-ASSOCIATED ANCA-ASSOCIATED VASCULITIS AT THE TIME OF TARGETED THERAPIES

Background:Several pharmacological classes are involved in drug-associated anti-neutrophil cytoplasmic antibody-associated vasculitis (DA-AAV). However, the literature data supporting the role a drug in the onset of DA-AAVs mainly rely on case reports or short series and implicate old treatments. Moreover, the advent of new treatments, including targeted therapies, may have modified the epidemiology of these adverse drug reactions (ADRs).Objectives:To update this list by using a pharmacovigilance-based data mining approach.Methods:We collected data on ADRs reported with the MedDRA preferred term “Anti-neutrophil cytoplasmic antibody positive vasculitis” up to November 2020, from the World Health Organization pharmacovigilance database. For each retrieved drug, a case/noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC025 value, which is the lower end of the 95% credibility interval, was considered significant.Results:A total of 483 deduplicated individual case safety reports of DA-AAV involving 15 drugs with an IC025&gt;0 were retrieved. DA-AAV occurred in 264 (71.2%, n=371) women, the median age at onset was 62 years [45-72], and the median time to onset between the introduction of the suspected drug and DA-AAV was 9 months [1-36]. DA-AAV occurrence was considered serious in 472 (97.7%, n=481) cases and fatal in 43 (8.9%) cases. The drugs associated with the highest disproportionate reporting were hydralazine, propylthiouracil, thiamazole, sofosbuvir, minocycline, carbimazole, mirabegron, and nintedanib (Table 1).Table 1.List of the 15 drugs associated with ANCA-associated vasculitis in the World Health Organization pharmacovigilance database with significant disproportional reporting, sorted by decreasing IC025.DrugNobservedNfatal (%)IC025 / ICROR [95%CI]Delay (in days) between the introduction of the drug and AAV, median [Q1-Q3] (n available)Hydralazine20819 (9%)8.2 / 8.42683.5 [2269.3-3173.3]1277 (n=1)Propylthiouracil1084 (4%)7.2 / 7.51201.5 [974.8-1480.9]1003 [425-1959] (n=19)Thiamazole405 (13%)5.2 / 5.6138.7 [100.7-191.1]411 [58-966] (n=6)Sofosbuvir4604.9 / 5.374.6 [55.3-100.8](n=0)Minocycline1703.8 / 4.672.4 [44.7-117.3](n=0)Carbimazole602.0 / 3.444.9 [20.1-100.4]92 (n=1)Mirabegron72 (29%)1.5 / 2.711.1 [5.3-23.3]291 [289-415] (n=3)Nintedanib62 (33%)1.4 / 2.814.2 [6.3-31.7]56 [36-132] (n=4)Penicillamine41 (25%)1.4 / 3.1170.3 [63.5-456.3](n=0)Influenza vaccine292 (7%)1.3 / 1.94.1 [2.8-6.0]24 [20-26] (n=7)Allopurinol72 (29%)1.2 / 2.48.0 [3.8-16.8](n=0)Rifampicin72 (29%)0.6 / 1.94.7 [2.2-9.8](n=0)Peginterferon alfa-2b400.3 / 2.17.0 [2.6-18.6]98 (n=1)Montelukast44 (100%)0.2 / 1.95.8 [2.2-15.5](n=0)Rosuvastatin600.1 / 1.53.4 [1.5-7.5](n=0)IC: information component; ROR: reporting odds ratio; CI: confidence interval; AAV: ANCA-associated vasculitisConclusion:This study strengthens the previously suspected association but also identifies 3 new drugs that may cause DA-AAV. Particular attention should be given to these drugs by prescribers and in experimental studies.Disclosure of Interests:None declared

Massive Alveolar Haemorrhage Presenting During the COVID-19 Pandemic

The coronavirus disease (COVID-19) pandemic has challenged healthcare systems and has resulted in complex diagnostic processes for patients with non-COVID-19 pathology. Here, we demonstrate a case of massive alveolar haemorrhage secondary to antineutrophil cytoplasmic antibody-positive vasculitis, presented to a district general hospital in the UK during the first wave of the global pandemic. This case highlights some of the difficulties clinicians may face when diagnosing life-threatening antineutrophil cytoplasmic antibody-positive vasculitis amidst the COVID-19 pandemic. The authors place emphasis on the careful interpretation of chemical biomarkers such as troponin and D-dimer when assessing patients with acute respiratory distress. They also aim to highlight the importance of CT thorax imaging when seeking an alternate diagnosis to COVID-19.

POS-156 MANAGEMENT AND OUTCOMES OF ANCA ASSOCIATED VASCULITIS AT A TERTIARY HEALTHCARE FACILITY

Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare disorder with annual incidence estimated to be around 1.3 per 100,000 population. Renal involvement is one of the main predictors of mortality and morbidity, with approximately 30% of patients with renal involvement progressing to ESRD after 5 years. Renal biopsy can provide a definite diagnosis, and may predict the renal prognosis in AAV. Limited data is available on its management and outcomes, thus we aim to assess this at our tertiary care renal facility. This was a retrospective cohort study. We included patients with a documented diagnosis of ANCA positive vasculitis between 1st of January 2012 to the 31st December 2017, with a follow up period until 31st December 2019. Using a standardized data collection form we recorded the number of patients who had a renal biopsy, the induction and maintenance therapies used, along with relapse induction and maintenance therapies. At the end of the follow-up period outcomes were divided into progression to end-stage renal disease (ESRD), death, established chronic kidney disease (CKD), and preservation of renal function. Data of thirty-six patients were included in the final study. The patient baseline characteristics are listed in Table 1. Thirty-two patients (94.1%) had a documented renal biopsy. The majority of patients (66.7%) had cyclophosphamide for induction, followed by rituximab (19.4%). Seven patients (19.4%) had a documented relapse during the study period, 4 MPO+ and 3 PR3+. Six patients (85.7%) had rituximab as an induction therapy for relapse. The majority of patients were on azathioprine (61.1%) as maintenance therapy after induction. This was similar to the maintenance therapy used after relapse (57.1%). Progression to ESRD occurred in 11 (30.6%), death in 4 (11.1%), established CKD in 15 (41.7%), and preservation of renal function in 6 (16.7%) patients by the end of the follow up period. While cyclophosphamide remains the choice of induction immunosuppresion therapy, we favour rituximab as an induction agent in relapse of AAV. However despite aggressive immunosuppresion therapy the incidence of ESRD and death remains high in these patients. The current management and outcomes are comparable to present international guidelines and cohorts. We look forward to new updates and therapies to improve outcomes in AAV.