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Introduction: Complement was long thought not to be involved in ANCA vasculitis pathogenesis until studies in murine models demonstrated its central role. The current theory is ANCA-activated neutrophils degranulate and release factors that activate complement, which, in turn, recruits more neutrophils and causes an inflammatory amplification loop that results in the vascular inflammation characteristic of disease. Targeting this amplification loop through complement inhibition has proven to be effective in ANCA vasculitis treatment. Areas covered: A PubMed search was conducted using key terms 'ANCA vasculitis' AND 'complement system.' We review the findings from experimental mouse models, in vitro studies, and human ANCA vasculitis that support a role for complement activation in disease pathogenesis. We also summarize results from pivotal clinical studies demonstrating the safety and efficacy of complement inhibition in ANCA vasculitis treatment. Expert opinion: While complement activation is undoubtedly involved in ANCA vasculitis pathogenesis, less clear is whether measuring complement activation markers can reliably assess disease activity, predict those who will benefit from complement-targeting therapy, or identify patients in stable remission and able to stop therapy. Better understanding the clinical implications of complement activation will shed more light on the utility of complement inhibition and facilitate precision medicine in ANCA vasculitis. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo report a complex case of serpiginous-like choroiditis (SLC) in a patient with anti-neutrophil cytoplasmic antibody (ANCA)-anti-proteinase 3 (PR3)-associated vasculitis with systemic involvement.Case report.A 40-year-old male from a tuberculosis (TB)-endemic region presented with bilateral active SLC lesions. He was diagnosed with ANCA-PR3 vasculitis with unilateral otitis media, nasopharyngeal mass, lung abscess, pleurisy, and joint pain, all of which responded well to corticosteroids and rituximab. Extensive evaluations and biopsies ruled out Mycobacterium tuberculosis infection. Despite consensus criteria recommending anti-tubercular therapy (ATT), the SLC lesions were effectively managed with an intravitreal dexamethasone implant and systemic azathioprine, showing no recurrence at 18 months without ATT.The development of SLC lesions in the context of systemic autoimmune conditions like ANCA-PR3 vasculitis is uncommon. In these cases, the need for ATT should be carefully evaluated, with close attention to systemic disease manifestations and tailored management strategies. [ABSTRACT FROM AUTHOR]

Microscopic polyangiitis (MPA) is a form of necrotizing vasculitis affecting the small vessels. Our study is the first study with the objective of describing the difference in clinical presentation of MPA and response to treatment at 6 months based on the age of disease onset. All patients seen at a tertiary vasculitis clinic between 2015 and 2023 with a diagnosis of MPA were included. Patients were divided into an elderly group (age > = 65 years) and a younger group (age < 65). Comparative analysis was conducted to characterize differences amongst the elderly and younger patients, including differences in organ involvement and clinical presentation, Birmingham Vasculitis Activity Score (BVAS) scores, Vasculitis Damage Index(VDI) scores, and response to treatment at 6 months. Thirty-one patients were included in our study. Younger MPA patients (n = 18) with mean age at diagnosis of 53.17 years were compared with older MPA patients(n = 13) with mean age at diagnosis of 76.08 years. The younger patients had statistically significant higher BVAS scores (p = 0.009), along with higher incidence of renal (p = 0.028), pulmonary (p = 0.0069), and cutaneous (p = 0.026) manifestations at disease onset. Furthermore, amongst the younger population, there was noted statistically significant clinical improvement at 6 months following treatment induction, particularly in the domains of general symptoms (p = 0.011), MSK (p = 0.019), cutaneous (p = 0.011), and pulmonary symptoms (p = 0.04). In contrast, the elderly population presented with a predominant of non-specific constitutional symptoms, with statistically significant improvement in the domain of non-specific general symptoms at 6 months (p = 0.00008). All MPA patients responded well to treatment, with statistically significant improvement amongst younger patients (p = 0.0032), but no statistically significant improvement amongst elderly patients (p = 0.67). Our study findings concluded that MPA's clinical presentation differed by age group. Younger patients had more aggressive vasculitis disease presentation with better response to treatments, whereas, elderly patients had less severe disease presentation with predominant of general symptoms at disease onset. Key Points • MPA clinical presentation differed by age at disease onset. Younger patients presented with more aggressive and classic vasculitis-like presentations, with multi-system organ involvement and statistically significant higher incidence of renal, pulmonary, and cutaneous manifestations. In contrast, elderly patients had a predominant of constitutional and non-specific symptoms with often delayed diagnosis. • All MPA patients responded well to treatment. Amongst the younger population, there was statistically significant improvement in BVAS scores after treatment induction at 6 months; however, there was no statistically significant improvement of BVAS scores in the elderly population. • Future studies are required to further understand the difference in the clinical presentation of MPA based on the age at disease onset, and the implication on disease diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Pauci-immune glomerulonephritis (PIGN) is typically secondary to antineutrophil cytoplasmic antibodies (ANCA) small-vessel vasculitis. However, some cases lack detectable circulating ANCA and are called ANCA-negative PIGN (seronegative PIGN). The reported incidence of this varies greatly. Its relationship to ANCA-associated vasculitis (AAV) is unclear. Summary: This review explores the pathophysiology of seronegative PIGN and summarizes findings from 12 studies focusing on this disease. The role of neutrophils appears to be central, with activation through cellular and humoral mechanisms. Most studies have noted less extrarenal involvement and more chronic changes in the kidney biopsy in seronegative PIGN compared to ANCA-positive cases. Studies have mostly reported using corticosteroids with cyclophosphamide for induction therapy and azathioprine for maintenance. The renal survival was noted to be lower compared to ANCA-positive PIGN. Key Messages: Whether ANCA-negative PIGN represents a distinct disease or is part of the AAV spectrum remains unclear. Prospective large-scale studies are needed to understand this disease for optimal diagnosis and management.

Severe infections associated with the use of strong immunosuppressive medication are a leading cause of morbidity and mortality in patients with ANCA vasculitis (AV). While guidelines conditionally recommend trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis jirovecii pneumonia in AV patients, robust evidence on prophylaxis strategies is lacking. This scoping review aimed to assess the existing evidence on infection prophylaxis in AV patients, identify knowledge gaps, and guide future study design. A comprehensive search of six databases and relevant references identified original studies in English from January 1, 2000, to July 31, 2020. Inclusion criteria encompassed studies evaluating the impact of any antimicrobial prophylaxis strategy on infection-related outcomes in AV patients receiving immunosuppressive treatment. Studies were screened by four researchers using a blinded approach. Data was extracted by two reviewers, with differences resolved via consensus in consultation with a third reviewer. Nineteen studies met inclusion criteria, including two randomized trials and 17 cohort studies, with TMP-SMX being the most commonly assessed prophylactic strategy. The studies varied in sample sizes, outcomes measured, prophylactic strategies employed, and proportion of patients who received the regimen. Most cohort studies included no or limited control of potential confounding factors. This scoping review suggests significant variation in AV patients' receipt of TMP-SMX and alternative infection prophylaxis approaches. Observational studies using large secondary healthcare databases with rigorous designs are needed to provide high-quality evidence of the real-world effectiveness of antimicrobial prophylactic regimens, to improve clinical decision-making and quality of care for AV patients receiving immunosuppressive treatment. Key Points • This study provides a comprehensive review of infection prophylaxis strategies for AV patients regardless of the immunosuppressants used, bridging the knowledge gap from prior systematic reviews that were exclusively focused only on TMP-SMX prophylaxis or the subset of AV patients receiving rituximab. • We included all studies evaluating the effectiveness of different prophylactic strategies with careful abstraction of sub-analyses reporting on outcomes of prophylaxis, even when such analyses were not the primary objective of published study reports. • We identified an opportunity for large secondary healthcare databases and target trial emulation techniques in future research to produce robust, real-world evidence on the effectiveness of antimicrobial prophylactic regimens to enhance clinical decision-making and improve the quality of care for AV patients. [ABSTRACT FROM AUTHOR]

Introduction: Although an increased risk of Pneumocystis jirovecii pneumonia (PJP) has been reported in adults receiving rituximab for induction therapy, current evidence is lacking on the utility of PJP prophylaxis in ANCA-associated vasculitis (AAV) patients on maintenance rituximab therapy. The purpose of this study was to compare the incidence of PJP pneumonia and the outcomes of AAV patients with and without PJP prophylaxis. Methods: We performed an observational, single-center, retrospective study examining patients with AAV in clinical remission and on rituximab maintenance therapy. We divided the patients into two groups: those with and without PJP prophylaxis. We explored factors associated with PJP prophylaxis use. We additionally looked at several outcomes, including PJP infections, infections requiring hospitalizations, end-stage kidney disease (ESKD), and death. Data were analyzed using T test, Fisher’s exact test, univariate, and multivariate logistic regression as appropriate. Results: A total of 129 patients with mean follow-up time of 7.2 (5.4) years were included: 44% received PJP prophylaxis and 56% of patients did not. There were no PJP infections in the entire cohort. Lung involvement was associated with increased odds of prescribing PJP prophylaxis (OR: 4.09 [95% CI: 1.8–9.82]). PJP prophylaxis did not decrease infection rates requiring hospitalizations, ESKD, or death. Glucocorticoid use, however, was associated with increased rates of infections requiring hospitalizations (OR: 5.54 [95% CI: 2.01–15.4]) and death (OR: 4.67 [95% CI: 1.36–15.71]) even after adjustment for age, gender, and use of PJP prophylaxis. Conclusion: Regardless of the use of PJP prophylaxis during the maintenance phase of AAV management, PJP pneumonia was not observed. AAV patients with lung involvement were more likely to be on PJP prophylaxis.

We describe the case of a 73-year-old man affected by pneumoconiosis, secondary to silica dust exposure, who was diagnosed with antineutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA)-related cervical myelitis. Pneumoconiosis is reported to trigger autoantibody production and the onset of different autoimmune diseases, including ANCA-associated vasculitis (AAV). MPA is an AAV of the small vessels that can often affect the nervous system, although involvement of the spinal cord in the form of myelitis is described as an anecdotal occurrence. Our experience suggests that an autoimmunity workup should be considered for patients with pneumoconiosis who present with neurological symptoms consistent with AAV.

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment.

Aim and background: This case report aims to highlight the atypical presentation of ANCA-associated vasculitis, where the patient experienced simultaneous occurrences of diffuse alveolar hemorrhage (DAH) and ileal perforation. ANCA-associated vasculitis is an autoimmune disorder that can lead to inflammation and damage of small blood vessels, resulting in various clinical manifestations. DAH is a common and severe pulmonary complication, while ileal perforation is a rare and life-threatening gastrointestinal complication. Case description: A 35-year-old male patient was admitted to the ICU with fever, dyspnea, and hemoptysis. He was diagnosed with MPO-positive ANCA vasculitis based on laboratory findings, and diagnostic tests. The patient's condition rapidly deteriorated, requiring invasive ventilatory support. He was treated with a combination of cyclophosphamide, rituximab, and high-dose corticosteroids. During treatment, he developed abdominal pain, dyspnea, and hypotension, and was found to have a small bowel perforation on imaging. The patient underwent emergency exploratory laparotomy, and the perforation was surgically repaired. Conclusion: This case highlights the atypical and severe manifestations of ANCA-associated vasculitis, with the occurrence of DAH and ileal perforation. The management of such complex cases requires a multidisciplinary approach, with prompt and aggressive treatment of the vasculitis and management of the complications. Clinical significance: This case emphasizes the importance of clinicians being aware of the potential for rare and atypical manifestations of ANCA-associated vasculitis. Early recognition and prompt intervention are crucial to improve patient outcomes. The case also need for further research to better understand the pathophysiological mechanisms and establish optimal treatment protocols for these rare complications. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary involvement is commonly observed in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presenting with manifestations such as diffuse alveolar hemorrhage, inflammatory infiltrates, pulmonary nodules, and tracheobronchial disease. We aimed to identify distinct subgroups of tracheobronchial disease patterns in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using latent class analysis (LCA), and to evaluate their clinical characteristics and outcomes. Methods: We conducted a retrospective cohort study using electronic medical records of patients aged >18 years diagnosed with AAV and tracheobronchial disease between 1 January 2002 and 6 September 2022. Patients with follow-up Results: Among 136 identified AAV patients assessed for tracheobronchial involvement, 111 (81.6%) were included after excluding 25 without tracheal or bronchial disease. Predominant findings included subglottic stenosis (91.0%), lower tracheal stenosis (16.2%), and bronchial stenosis (17.1%). LCA identified a three-class model as optimal: tracheal predominant (n = 94), tracheobronchial (n = 12), and bronchial predominant (n = 5). Tracheal predominant patients showed reduced risk of ear, eye, and lower respiratory manifestations, with milder obstruction on pulmonary function testing (PFT). Tracheobronchial-class patients were prone to saddle nose deformity (50%), extensive lower respiratory involvement (91.7%), and renal disease (66.7%). Bronchial predominant patients exhibited severe obstructive disease (median forced expiratory volume in 1 s (FEV1)% predicted: 58, IQR 34–66; FEV1/forced vital capacity (FVC) ratio: 56.9, interquartile range (IQR) 43–63.3) but lacked systemic AAV manifestations. LCA classes did not predict outcomes such as endoscopic intervention, tracheostomy, recurrent tracheobronchial narrowing, or mortality. Conclusion: LCA shows promise in subtype stratification of AAV patients, yet its utility in predicting outcomes and guiding treatment remains limited based on our analysis. Future studies with enhanced phenotypic data and larger cohorts are warranted to improve predictive accuracy.

Background: Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. Methods: Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. Results: a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. Conclusions: GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up. [ABSTRACT FROM AUTHOR]

The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011–2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease. We defined cohorts as those who relapsed (Relapse Cohort) and controls as those who did not relapse (Remission Cohort) during the study period. Survey responses were retrospectively reviewed during a 15-month timeframe prior to relapse or during 15 months of remission and categorized by type of stress event, insect bite, and infections at every available 3-month interval. There were no significant differences in stress and insect bites between the relapse and remission cohorts. Patients who relapsed reported more frequent upper respiratory infections and other infections, such as those affecting the skin and eyes, but there were no significant differences in the incidence of pulmonary or urinary infections compared to the remission cohort. There was a significant difference in reported upper respiratory infections 9 to 15 months prior to the relapse date, indicating a remote history of infections as a potentially significant physical stressor that may contribute to disease relapse. More frequent patient-reported infections, specifically upper respiratory infections, may contribute to patient vulnerability to relapse. Counseling and close monitoring of patients after infectious symptoms could aid in earlier detection of disease flares. Future studies are essential to further understand the importance of distal risk factors and how they impact relapse.

The advent of COVID-19, caused by the SARS-CoV-2 virus, has resulted in over 541 million cases with 6.32 million deaths worldwide as of June 2022. The devastating consequences of this global pandemic resulted in the expedited generation of mRNA-based vaccines such as the Pfizer-BioNTech and Moderna vaccines. Although the vaccines have been effective, with recent data indicating greater than 95% effectiveness, rare complications have been reported, including manifestations of autoimmune phenomena. Herein, we report a rare case of Granulomatosis with polyangiitis (GPA) in an active duty military male soon after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine.

Purpose of Review: Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare, multisystem, autoimmune disease characterised by microvascular inflammation. Over the past 20 years, advances in immunological management have improved short-term patient outcomes. Longer-term patient outcomes remain poor with cardiovascular disease now the leading cause of death in AAV. Here, we examine the potential pathways that contribute to the increased risk of cardiovascular disease in AAV and the current evidence to manage this risk. Recent Findings: The incidence of cardiovascular disease in AAV exceeds that expected by traditional risk factors alone, suggesting a contribution from disease-specific factors. Similarly, it is unclear how different immunosuppressive therapies contribute to and modify cardiovascular risk, and there is a paucity of data examining the efficacy of traditional cardioprotective medications in AAV. Summary: There is a lack of evidence-based cardiovascular risk assessment tools and cardioprotective therapies in patients with AAV which should be addressed to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment. [ABSTRACT FROM AUTHOR]

Circulating endothelial progenitor cells (EPCs) were first described in 1997 by Asahara et al. as "putative endothelial cells" from human peripheral blood. The study of endothelial progenitors is also intensifying in several pathologies associated with endothelial damage, including diabetes, myocardial infarction, sepsis, pulmonary arterial hypertension, obstructive bronchopneumopathy and transplantation. EPCs have been studied in several autoimmune diseases with endothelial involvement such as systemic lupus erythematosus, thrombotic thrombocytopenic purpura, antineutrophil cytoplasmic antibodies, vasculitis, rheumatoid arthritis, Goujerot-Sjögren and antiphospholipid syndrome. Factors involved in endothelial damage are due to overexpression of pro-inflammatory cytokines and/or autoantibodies. Management of these pathologies, particularly the long-term use of glucocorticoids and methotrexate, promote atherosclerosis. A lack of standardized assessment of the number and function of EPCs represents a serious challenge for the use of EPCs as prognostic markers of cardiovascular diseases (CVD). The objective of this review was to describe EPCs, their properties and their involvement in several autoimmune diseases. [ABSTRACT FROM AUTHOR]

Abstract Background The occurrence of autoantibodies in human immunodeficiency virus (HIV)-infected patients has been previously reported, with a prevalence ranging from 20 to 83%. There are also a few reports of clinically relevant autoantibody profiles in HIV-positive patients that lead to true systemic autoimmune disease; these possible life-threatening diseases have to be considered and treated accordingly. Case presentation Here, we present the case of a 29-year-old female patient with a history of well-controlled HIV infection in the last 6 years who was admitted to our department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. A diagnosis of systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal and pulmonary involvement was established. The patient was treated with cyclophosphamide, rituximab and tapering glucocorticoids,and the diffuse alveolar hemorrhage resolved, but the evolution of kidney function was unfavorable, which led to the need to initiate hemodialysis. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear in a patient with HIV infection during immunosuppressant treatment as induction treatment. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence. Conclusions Although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV.

Vasculitis and HIT have different etiologies, although both involve autoimmune mechanisms. Treatment of vasculitis often requires the use of an anticoagulant such as heparin, which can lead to the development of HIT and subsequent life-threatening complications. The analysis covered patients hospitalized in the Department of Internal Medicine, Nephrology and Dialysis in the period from September 2020 to March 2023. After analyzing the data, we selected four patients in whom vasculitis treatment was complicated by HIT. These included two patients with ANCA vasculitis and two patients with anti-GBM disease. We also described similar cases reported in the literature. [ABSTRACT FROM AUTHOR]

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Background: The occurrence of autoantibodies in human immunodeficiency virus (HIV)-infected patients has been previously reported, with a prevalence ranging from 20 to 83%. There are also a few reports of clinically relevant autoantibody profiles in HIV-positive patients that lead to true systemic autoimmune disease; these possible life-threatening diseases have to be considered and treated accordingly. Case presentation: Here, we present the case of a 29-year-old female patient with a history of well-controlled HIV infection in the last 6 years who was admitted to our department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. A diagnosis of systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal and pulmonary involvement was established. The patient was treated with cyclophosphamide, rituximab and tapering glucocorticoids,and the diffuse alveolar hemorrhage resolved, but the evolution of kidney function was unfavorable, which led to the need to initiate hemodialysis. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear in a patient with HIV infection during immunosuppressant treatment as induction treatment. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence. Conclusions: Although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV. [ABSTRACT FROM AUTHOR]

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) is one of three described anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Early diagnosis and treatment of GPA is paramount, as it may help prevent irreversible end-organ damage, especially renal and pulmonary failure. A 72-year-old male with a past medical history of lung adenocarcinoma in remission, chronic sinusitis status-post multiple sinus surgeries, and coronary artery disease presented with shortness of breath, dark urine, and asymmetric polyarthralgias. He had an acute kidney injury, leukocytosis, with urinalysis demonstrating pyuria and hematuria, without casts. Chest imaging showed cavitary nodular opacities in addition to interval increase of existing nodules compared to the most recent scan one month prior. His acute kidney injury progressed to renal failure requiring hemodialysis, and he developed an inflammatory polyarthritis. GPA was suspected clinically so he was started on high-dose intravenous corticosteroids, and subsequently plasmapheresis and rituximab. Serology returned with highly positive proteinase-3 antibodies, and cytoplasmic ANCA positivity on immunofluorescence. Renal biopsy demonstrated severely active pauci-immune glomerulonephritis. Several months after discharge, the patient passed away from gram positive bacteremia. This patient's recurrent sinusitis, pulmonary nodules, and subsequent renal failure were highly suggestive of GPA. A biopsy is recommended to confirm the diagnosis of GPA, but treatment should not be delayed if there is a high index of suspicion for the disease. Induction therapy with corticosteroids combined with rituximab or cyclophosphamide has significantly decreased the mortality of patients with GPA. Patients with GPA often have preceding history of nasopharyngeal and upper airway disease, and can present with fluctuating pulmonary infiltrates. Early recognition and treatment of patients with GPA can prevent life-threatening complications and reduce mortality.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a combined immunodeficiency with a broad clinical phenotype, including not only an increased propensity for sinopulmonary and herpesviruses infections but also immune dysregulation, such as benign lymphoproliferation, autoimmunity, and malignancy. Autoimmune complications are increasingly recognized as initial presenting features of immune dysregulation in inborn errors of immunity (IEIs), including APDS, so awareness of the spectrum of autoimmune features inherit within these disorders is critical. We present here a patient vignette to highlight cutaneous antineutrophil cytoplasmic antibody (ANCA) vasculitis as an underrecognized autoimmune manifestation of APDS. The genetic defects underlying APDS result in increased PI3Kδ signaling with aberrant downstream signaling pathways and loss of B- and/or T-cell immunologic tolerance mechanisms, which promote the development of autoimmunity. An understanding of the molecular pathways and mechanisms that lead to immune dysregulation in APDS has allowed for significant advancements in the development of precision-medicine therapeutics, such as leniolisib, to reduce the morbidity and mortality for these patients. Overall, this case and review highlight the need to maintain a high index of suspicion for IEIs, such as APDS, in those presenting with autoimmunity in combination with a dysregulated immune phenotype for prompt diagnosis and targeted intervention.

Objective : Diffuse alveolar hemorrhage (DAH) is a severe pulmonary complication of numerous diseases, including rheumatic conditions. We have conducted an observational study using inpatient data from the National Inpatient Sample to study the relationship of DAH with rheumatic conditions along with their descriptive characteristics. Methods: An observational study was conducted on hospitalizations in 2016–2018 with a principal diagnosis of DAH from the United States National Inpatient Sample database. A multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORadj) for risk factors of DAH. Results: A total of 5420 DAH hospitalizations were identified among 90 million hospitalizations. Mortality in this group was found to be 24.3%. Majority of patients admitted with DAH were white and male, with a mean age of 61.8 years and a mean LOS of 10.6 days. Multivariate analysis showed that multiple rheumatic diseases were associated with DAH, including anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) (ORadj 72.56) (95% C.I. 50.607–104.043), antiphospholipid antibody syndrome (APLS) (ORadj 6.51) (95% C.I. 3.734–11.366), eosinophilic granulomatosis with polyangiitis (EGPA) (ORadj 7.13) (95% C.I. 1.886–26.926), Goodpasture's (ORadj 30.58) (95% C.I. 16.360–57.176), rheumatoid arthritis (RA) (ORadj 1.60) (95% C.I. 1.158–2.212), sarcoidosis (ORadj 3.99) (95% C.I. 2.300–6.926), and systemic lupus (SLE) (ORadj 5.82) (95% C.I. 3.993–8.481). Conclusion: Although DAH is a relatively rare entity, it carries a very high mortality. Multiple rheumatic diseases were associated with DAH hospitalizations including AAV, APLS, EGPA, Goodpasture's, RA, sarcoidosis, and SLE. Key points • It is known that DAH carries a high morbidity and mortality based on prior literature. However, large datasets on the association of rheumatic diseases with DAH are lacking • This study identifies the descriptive characteristics of patients admitted to the hospital with DAH • This study also identifies the strength of association of rheumatic diseases with DAH [ABSTRACT FROM AUTHOR]

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases. [ABSTRACT FROM AUTHOR]

Procalcitonin (PCT) was established as a biomarker to discriminate bacterial infections from other proinflammatory conditions. Our objective was to determine whether PCT is effective in differentiating infection from antineutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAV) flare. In this retrospective, case-control study, PCT and other inflammatory biomarkers of patients with AAV relapse (relapsing group) were compared to infected AAV patients (infected group). In our population of 74 patients with AAV, PCT was significantly higher in the infected group than in the relapsing group (0.2 µg/L [0.08; 0.935] vs. 0.09 µg/L [0.05; 0.2], p < 0.001). Sensitivity and specificity were 53.4% and 73.6%, respectively, for an ideal threshold of 0.2 µg/L. C-reactive protein (CRP) was significantly higher in cases of infection than in relapse (64.7 mg/L [25; 131] vs. 31.5 mg/L, [10.6; 120], p = 0.001). Sensitivity and specificity for infections were 94.2% and 11.3%, respectively. Fibrinogen, white blood cell count, eosinophil count, and neutrophil count were not significantly different. In the multivariate analysis, the relative risk of infection was 2 [1.02; 4.5] (p = 0.04) for a PCT above 0.2 µg/L. In AAV, PCT may be useful for discriminating between infections and flare in patients suffering from AAVs. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the role of nasal Staphylococcus aureus (S. aureus) colonization and the effect of systemic or local antibiotic treatment on disease activity in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and ear nose and throat (ENT) involvement. Clinical, laboratory and histological data from all patients with ANCA-associated vasculitis and ENT involvement, who were diagnosed in two medical centres in The Netherlands between 1981 and 2020, were retrospectively collected. Nasal S. aureus colonization was defined as at least one positive nasal swab during follow-up. Data on systemic (cotrimoxazole and azithromycin) and local (mupirocin) antibiotic use were collected. Disease activity was divided into systemic and local disease activity. Univariate analyses and regression analyses (negative binomial Poisson and binary regression) were used. Two-hundred and thirteen patients were available for analysis. Median follow-up time was 8 (IQR 3–17) years. S. aureus colonization was tested in 100 (46.9%) cases of whom 44 patients (44%) tested positive. In these 100 patients, systemic and local disease activity at baseline and at last visit were comparable between patients with and without S. aureus colonization. Twenty-eight of the 44 S. aureus positive patients received antibiotics aimed at eradication of S. aureus. No statistically significant difference was found between the treated versus non-treated group with regard to systemic and local disease activity. Nasal S. aureus colonization does not influence systemic or local disease activity. Antibiotic treatment aimed at eradication did not modify disease activity. [ABSTRACT FROM AUTHOR]

Hydralazine is an antihypertensive medication that has been associated with drug-associated autoimmune syndromes like interstitial lung disease, pauci-immune glomerulonephritis, and hypocomplementemia. Hydralazine-induced ANCA-associated vasculitis and hydralazine induced positive antinuclear antibodies are rare. Clinical manifestations range from arthralgia, petechiae, or rash to multiorgan involvement. When presented as pulmonary-renal syndrome, it can be rapidly progressive and fatal. Here, we describe a case of hydralazine-associated vasculitis with rapidly progressive glomerulonephritis and highlight the importance of early diagnosis and prompt treatment. [ABSTRACT FROM AUTHOR]

Patients with antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis who were on immunosuppressive therapy with corticosteroids may be susceptible to cavitary lesions. 1 Only a few cases have been reported in the literature to date. Immunosuppression was shown to improve prognosis in patients with vasculitis. However, adverse therapy events and the risk of opportunistic infections become a major cause of morbidity and mortality in this specific patient population. We present a case of a 75-year-old female who was diagnosed and treated in our hospital for ANCA-associated vasculitis and returned within a few weeks of medical therapy and was found to have developed cavitation concerning for worsening vasculitis or an opportunistic fungal infection or combination of both. Given the risk of severe complications from opportunistic fungal infections, close monitoring and prophylactic antifungal therapy should be considered. Further studies are needed to evaluate the benefit of prophylaxis in this patient population. [ABSTRACT FROM AUTHOR]

Malgré l'avènement de la pathologie moléculaire et l'émergence des biomarqueurs non invasifs, le rôle de l'histopathologie dans le diagnostic et la classification des maladies reste majeur en pathologie inflammatoire, et en particulier en néphrologie. Dans cette revue, nous utiliserons l'exemple des vascularites associées aux anticorps anti- cytoplasme des polynucléaires neutrophiles (ANCA), pour illustrer le rôle de l'anatomie pathologique dans la détermination du pronostic en pathologie inflammatoire. Despite the advent of molecular pathology and the emergence of non-invasive biomarkers, the role of histopathology in the diagnosis and classification of diseases remains crucial in inflammatory diseases, particularly in nephrology. In this review, we will illustrate the role of anatomopathology to determine the prognosis in inflammatory disorders, through the example of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. [ABSTRACT FROM AUTHOR]

Objectives: T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self‐harming immune responses and prevent the development of autoimmune diseases. In anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice‐variant lacking exon 2 in T cells (FOXP3Δ2 CD4+ T cells). However, the suppressive capacity of Tregs varies between subsets. We evaluated the frequency of Treg subsets in ANCA vasculitis as a potential explanation for diminished suppressive capacity. Methods: We developed a custom mass cytometry panel and performed deep immune profiling of Tregs in healthy controls, patients with active disease and in remission. Using these data, we performed multidimensional reduction and discriminant analysis to identify associations between Treg subsets and disease activity. Results: Total Tregs were expanded in ANCA vasculitis, which was associated with remission and the administration of rituximab and/or prednisone. The frequency of FOXP3Δ2 CD4+ T cells did not distinguish disease activity and this population had high expression levels of CD127 and lacked both CD25 and Helios, suggesting that they are not conventional Tregs. The frequency of CXCR3+, CD103+ and CCR7+ Tregs distinguished disease activity, and the combination of the frequency of these three Treg subsets segregated active patients from patients in remission and healthy controls. From these three subsets, the frequency of CXCR3+ Tregs distinguished patients with active disease with renal involvement. Conclusion: Treg heterogeneity can discriminate disease activity and should be explored as a biomarker of disease activity in ANCA vasculitis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized solid organ and hematologic cancer treatments by improving overall prognoses. However, they can lead to overactivation of the immune system and several immune-related adverse events and sometimes affecting the renal system. Although acute interstitial nephritis is well described, we know little about ICI-associated glomerular injury. Herein, we report an exceptional case of renal ANCA positive-associated vasculitis (AAV) after nivolumab therapy. Three weeks after the last nivolumab injection, the patient presented with proteinuria at 1.73 g/g of creatininuria, hematuria, and acute kidney injury needing dialysis associated with lung hemorrhage; anti-neutrophil cytoplasmic antibody (ANCA titer ≥1,280 with myeloperoxidase specificity of 780 U/mL) was positive, and kidney biopsy confirmed glomerular injury with crescents. The patient underwent treatment with steroid pulses, rituximab, and plasmapheresis, resulting in an improvement of the renal function and lung hemorrhage and produced a negative ANCA titer. Despite the results of the PEXIVAS study and the absence of clear benefit of plasmapheresis demonstrated in idiopathic AAV, we suggest that drug-induced AAV may be effectively treated by plasmapheresis, steroids, and rituximab.

Ameboma refers to the rare development of an inflammatory, ulcerated, exophytic mass in the gastrointestinal tract that can resemble carcinoma. Typically it presents as a right lower quadrant abdominal mass, Patients may also present with diarrhea or constipation and associated systemic symptoms, including weight loss and fever. In this article we present a young man with a background of ANCA associated vasculitis, who presented with fresh lower gastrointestinal bleeding during hospital admission for severe covid-19 pneumonia which turned out to be caecal aemboma. This case is highlighted for its rarity, the diagnostic challenge, and for the major role of colonoscopy as a diagnostic tool for this pathology.

• Rapid taper of glucocorticoids in the management of ANCA vasculitis without compromising efficacy. • Novel therapies in the management of ANCA vasculitis. • Role of AVACOPAN in the management of ANCA vasculitis. • Targeting C5a receptors shows efficacy in the management of ANCA vasculitis. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis comprises a rare entity of disorders that affects primarily small and medium-sized blood vessels. Since first documented in 1897, we have come a long way trying to understand the pathogenesis and finding an optimal treatment regimen. The pathogenesis of ANCA vasculitis is not well understood and despite many advances in treatment, the morbidity and mortality remains high. Over the last decade, there have been many advancements toward elucidating the pathogenesis, optimizing current therapies, and discovering new medicines. Presently, one trend is aimed at minimizing the adverse effects of glucocorticoids by reducing their use without sacrificing efficacy and safety. A new medicine targeting the alternative complement system has emerged and intends to replace glucocorticoids. Here, we review three articles that describe these new trends in the management of ANCA vasculitis. [ABSTRACT FROM AUTHOR]

Background. Data concerning central nervous system (CNS) alterations in ANCA-associated vasculitis with renal involvement (AAVR) are sparse. The study aimed to assess vascular and vasogenic brain alterations in patients with acute onset of AAVR and the applicability of non-contrast magnetic resonance imaging (MRI) techniques in this diagnosis. Methods. Thirty-eight patients with acute onset of AAVR were included in the study. BVAS/WG, c-ANCA, p-ANCA, renal function and perfusion, neurological assessment, and brain MRI were performed. Results. Cerebral vascular alternating narrowing and dilatation (VAND) was detected in 42.1% of patients, and the black-blood was significantly more diagnostic than the TOF technique (p < 0.001). VAND occurrence was independently associated with the concentration of p-ANCA. The vasogenic white matter lesions (VWML) were found in 94.4% of patients, and in their detection, SWAN was significantly better than the FLAIR technique (p = 0.002). The number of VWML correlated with age and cranial nerve damage. Hemosiderin deposits were found in 21.6% of patients and were associated with a gait impairment and paresthesia. Conclusions. Vascular and vasogenic alterations in the CNS are frequent in patients with acute onset of systemic ANCA-associated vasculitis with renal involvement. Non-contrast MRI is useful in the diagnosis of brain vasculitis. [ABSTRACT FROM AUTHOR]

The paper describes a clinical case of pulmonary and right orbital injuries in granulomatosis with polyangiitis in a 38-year-old male. The case is of considerable interest due to the rarity of this pathology, especially because of the localization in the orbital region. The information provided in this paper can help in the early and accurate diagnosis of granulomatosis with polyangiitis, which, in turn, will improve the prognosis of the disease.

In the last two years, our world experienced one of the most devastating and fast-exploding pandemic, due to the wide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The scientific community managed to develop effective vaccines, the main weapons to shield the immune system and protect people. Nevertheless, both SARS-CoV-2 infection and the vaccination against it have been associated with the stimulation of inflammatory cells such as T and B lymphocytes that results in a cytokine storm, endothelial inflammation and vascular injury, which can lead to different types of vasculitis. We present the first case of de novo MPO-ANCA-associated vasculitis, which developed shortly after SARS-CoV-2 vaccination, adequately responded to treatment, and subsequently relapsed after COVID-19 infection. With this case, we indicate an etiological connection between viral infection and disease development, as well as the possibility of a common immune mechanism between SARS-CoV-2 infection and vaccination, that can stimulate vascular events and lead to vasculitis. There have been several case reports of de novo vasculitis, affecting large, medium, or small vessels, following either infection or vaccination against COVID-19, during the pandemic outbreak. We summarize previous reports and also analyze proposed pathogenic mechanisms between SARS-CoV-2 and vasculitis. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a rare condition in pediatric patients. Little is known about practice patterns and outcomes of pediatric transplant patients. The purpose of our study was to examine differences in patient characteristics, immunosuppression, and long-term graft outcomes between ANCA and non-ANCA vasculitis recipients. Methods: We used the Scientific Registry of Transplant Recipients to evaluate pediatric ANCA vasculitis recipients between the ages of 1 and 22 years old from 1991 to 2017 and compared them to non-ANCA vasculitis patients during the same time cohort in the USA. Results: A total of 26,431 transplant recipients were identified, of these, 337 with ANCA vasculitis. Mean 1-year eGFR was 62.46 and 64.92 ml/min/1.73 m2 (p = 0.002), and mean 5-year eGFR was 57.95 and 59.38 ml/min/1.73 m2 (p = 0.18) between the non-ANCA and ANCA groups, respectively. Five-year graft survival was similar in both groups (non-ANCA 75.5 vs. ANCA 78.6%; p = 0.19). Of those with graft loss within the ANCA group, only 0.6% was secondary to disease recurrence (p = 0.14). Conclusions: Kidney transplant is a safe treatment modality for children with ANCA-related kidney failure. ANCA patients have comparable graft survival when compared to the general transplant population with a low risk of recurrence. Thymoglobulin was used in a higher proportion within the ANCA group compared to the non-ANCA group. Tacrolimus, mycophenolate mofetil/mycophenolic acid, and steroids were the predominant maintenance immunosuppression used in both groups. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. Methods We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed. Results Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P < 0.0001). In multivariate Cox analysis, lymphopaenia was an independent risk factor for ESKD [hazard ratio 4.47 (95% confidence interval 2.06–9.72), P < 0.001]. Conclusions Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis. [ABSTRACT FROM AUTHOR]

The discovery of anti-neutrophil cytoplasmic antibodies (ANCA) and their antigenic targets, myeloperoxidase (MPO) and proteinase 3 (PR3), has led to further understanding as to the pathophysiologic processes that underlie vascular and tissue damage in ANCA vasculitis. ANCA trigger neutrophil activation leading to vascular damage in ANCA vasculitis. However, decades of study have determined that neutrophil activation alone is not sufficient to cause disease. Inflammatory stimuli are drivers of ANCA autoantigen expression and ANCA production. Certain infections or bacterial peptides may be crucial players in the initial steps of ANCA immunopathogenesis. Genetic and epigenetic alterations of gene encoding for MPO and PR3 provide additional disturbances to the immune homeostasis which provide a substrate for pathogenic ANCA formation from an adaptive immune system predisposed to autoreactivity. Promoted by inflammatory cytokines, ANCA binding leads to neutrophil activation, a process characterized by conformational changes, production and release of cytotoxic substances, and alternative complement pathway activation, thus creating an intense inflammatory milieu. This cascade of events perpetuates a vicious cycle of further inflammatory cell recruitment and activation, culminating in tissue necrosis. Our understanding of the pathogenic process in ANCA vasculitis paves the way for the development of therapies targeting crucial steps in this process. The greater appreciation of the role for complement, monocytes, and the adaptive immune system has already led to novel complement blockers and is poised to lead to further innovations which will allow for tailored antigen- or cell-specific immunotherapy targeting the autoimmune process without exposure to undue risks or toxicities. [ABSTRACT FROM AUTHOR]

Objectives ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV. Methods In a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients. Results We identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician's impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data. Conclusion Interval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV. [ABSTRACT FROM AUTHOR]

Abstract Background Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors—after the introduction of B cell depleting agents—are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort. Methods Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers. Results We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001–9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93–14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01–1.21) was associated with SI only during the 1st year. Conclusions In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.

Azathioprine (AZA) drug hypersensitivity reaction (DHR) is an uncommon yet potentially lethal condition that often goes unrecognised in patients with anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV). We conducted a retrospective review of AAV patients on AZA maintenance therapy (N = 35). Participants were categorised into those who had experienced AZA-DHR (N = 15) and those who were AZA-tolerant (N = 20). Human leukocyte antigen (HLA) typing was performed in both groups. The primary endpoint was identification of a HLA gene association with AZA-DHR in the context of AAV. HLA-C*06:02, was solely expressed in AZA-DHR patients (33.3 %), whilst no patient who tolerated AZA carried this allele (0.0 %). This yielded a positive predictive value of 100 % for HLA-C*06:02 in predicting AZA-DHR in AAV patients, negative predictive value of 66.7 %, sensitivity of 33.3 % and specificity of 100 %. HLA-C*06:02 may predict the development of AZA-DHR in patients with AAV and inform safer therapeutic choice. [ABSTRACT FROM AUTHOR]

Introduction: ANCA-associated vasculitis is a disease with high morbidity and mortality which has shown to have different phenotypes in different ethnic and racial groups. This disease has been most frequently studied in Caucasians. We studied a group in Southern California where the Hispanics make up half of the population. We believe there will be different phenotypes between the two. Methods: A retrospective study of 114 patients was conducted at two tertiary care centers between 2003 and 2019. Demographic data, ICU admission, ANCA antibody status, BVAS on presentation, VDI per the last clinic visit, the number of hospitalizations, the number of follow-up years, and treatment were recorded. We calculated odds ratios for the categorical data and ran independent sample T test for the continuous data with alpha equal to 0.05 for statistical significance. Results: Difference was found in antibody status, disease presentation, morbidity, and age at diagnosis. Hispanics had greater number of AAV flares despite BVAS and VDI being comparable. Caucasians had more frequent follow-up. Hispanics had a 4.39 increase in odds of being admitted to the ICU, a 1.33 increased odds of developing acute respiratory failure, and a 67% increased odds of developing hemoptysis or pulmonary alveolar hemorrhage. Further, Hispanics had a 1.22 increase in odds of having ESRD. Conclusions: Clinicians treating Hispanic patients with AAV should have a high index of suspicion for severe disease in this patient population. Further, epidemiologic and disparities research should be conducted to evaluate the discrepancy in outcomes in these groups. Key Points • This is the first study to examine the phenotype and severity of ANCA associated vasculitis in Southern California, a population which is comprised largely of Hispanics. • Hispanics in this population were found to be more likely to be admitted to the ICU, have more flares, reach end-stage renal disease, have severe pulmonary manifestations, and had fewer outpatient follow-up visits than their Caucasian counterparts. • Clinicians should have a high suspicion for more severe disease in Hispanics in this region when compared to Caucasians. • More research is needed to assess the degree social determinants of health contribute to these findings and if progress can be made with decreasing health disparities between these populations in this disease. [ABSTRACT FROM AUTHOR]