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Objective: This study explored the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its risk factors in patients with idiopathic interstitial pneumonia (IIP) and positive ANCA results., Methods: Data of patients diagnosed with IIP with positive ANCA results at a single tertiary center in South Korea were retrospectively reviewed from January 2013 to August 2023. Cox regression analysis was performed to identify variables associated with AAV occurrence following IIP diagnosis. Kaplan-Meier curves were employed to investigate the relationship between autoantibodies and the occurrence of AAV., Results: In a cohort of 154 IIP-diagnosed patients with positive ANCA results but without AAV, 10.4 % of them eventually developed AAV. The AAV and non-AAV groups did not significantly differ by sex, age, smoking status, urinalysis, or chest computed tomography findings. All the patients who subsequently developed AAV were anti-myeloperoxidase (MPO) positive, while 48.8 % of the non-AAV patients were anti-MPO positive (P < 0.001). Rheumatoid factor (RF) positivity differed significantly (62.5 % vs. 29.2 %, P = 0.007) between the AAV and non-AAV groups. Multivariate Cox regression and Kaplan-Meier analyses revealed RF (HR 4.02; P = 0.004) and anti-MPO (HR 38.10; P < 0.001) positivity as risk factors associated with AAV occurrence., Conclusion: Approximately 10 % of ANCA-positive IIP patients developed AAV after an IIP diagnosis. Anti-MPO or co-occurring positive RF poses a significant risk for subsequent AAV occurrence. This emphasizes the importance of careful monitoring in patients with high-risk antibody profiles, even if the complete features of AAV are not present at IIP diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases., Methods: Case report., Results: A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments., Conclusion: Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis.

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort., Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death., Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12-17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome., Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Competing Interests: None.

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., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations., Methods: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients., Results: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement., Conclusion: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Pulmonary haemorrhage with hypoxia caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) Trial., Methods: A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan., Results: Eight patients (62.5% female), median age 64 years (range 17-80), seven with kidney involvement, median estimated glomerular filtration rate (eGFR) 11 (range 5-99) mL/min/1.73 m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were myeloperoxidase-ANCA and three proteinase 3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6-60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received 2 months of daily extracorporeal membrane oxygenation therapy. Following the initiation of avacopan after a median of 10 days (range 2-40), pulmonary haemorrhage resolved in all patients, even the two who had 1 month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after 1 month, the median prednisolone dose was 5 mg/day (range 0-50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after 3 months due to neutropenia. All patients survived and no re-hospitalization occurred., Conclusion: We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV., Methods: The dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995-2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs., Results: The cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years.In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P < .001 and P = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71-0.83)., Conclusions: Early diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Several scores have been developed to predict mortality at anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none has been developed in this specific population. We aimed to propose a novel and more accurate score specific for them., Methods: This multicentric study included patients diagnosed with AAV-GN since January 2000 in four nephrology centers (recorded in the Maine-Anjou AAV-GN Registry). Existing scores and baseline characteristics were assessed at diagnosis before any therapeutic intervention. A multivariable analysis was performed to build a new predictive score for death. Its prognosis performance (area under receiving operating curve and C-index) and accuracy (Brier score) was compared with existing scores. One hundred and eighty-five patients with AAV-GN from the RENVAS registry were used as a validation cohort., Results: A total of 228 patients with AAV-GN from the Maine-Anjou registry were included to build the new score. It included the four components most associated with death: age, history of hypertension or cardiac disease, creatinine and hemoglobin levels at diagnosis. Overall, 194 patients had all the data available to determine the performance of the new score and existing scores. The new score performed better than the previous ones in the development and in the validation cohort. Among the scores tested, only Five-Factor Score and Japanese Vasculitis Activity Score had good performance in predicting death in AAV-GN., Conclusions: This original score, named DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk), may be useful to predict the risk of death in AAV-GN patients. Validation in different populations is needed to clarify its role in assisting clinical decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objectives: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Methods: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022., Results: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group ( P <0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group ( P <0.05)., Conclusions: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.

Background: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV., Methods: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022., Results: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007)., Conclusions: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases., (© 2024. The Author(s).)

Purpose of Review: Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis., Recent Findings: Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Granulomatosis with polyangiitis (GPA) is a pauci-immune vasculitis typically involving upper and lower respiratory tract involvement and crescentic glomerulonephritis. Salivary gland involvement in GPA is rare. When it occurs in GPA, it is commonly seen with sinonasal and lung involvement and rarely with renal involvement. Easy accessibility of salivary glands allows early biopsy and timely treatment. In our case with GPA, salivary gland involvement was unresponsive to cyclophosphamide but remitted with rituximab., (© Journal of the Association of Physicians of India 2024.)

Objective: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management., Methods: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type., Results: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %)., Conclusion: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Relapses are frequent and difficult to predict in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), resulting in long-term use of immunosuppression. Although sinonasal disease is associated with relapse of AAV, detailed characterization of sinonasal symptoms is lacking. Using a patient-reported outcome, the 22-item SinoNasal Outcome Test (SNOT-22), we investigated the relationship between sinonasal symptoms and disease activity in AAV., Methods: This was a prospective, longitudinal study of individual with AAV and healthy individuals. Relapse was defined as a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis score >0. Higher SNOT-22 scores indicate worse symptoms. Generalized estimating equation and Cox proportional hazard models evaluated the association between SNOT-22 and relapse., Results: There were 773 visits (106 active disease visits) from 168 patients with AAV and 51 controls. Median SNOT-22 at remission was higher in AAV versus controls (20 vs 5; P < 0.001) and higher during active disease versus remission (P < 0.001). In all AAV, and particularly within granulomatosis with polyangiitis, higher SNOT-22 scores were observed months to years before relapse and were associated with increased risk of relapse (hazard ratio 2.7, 95% confidence interval 1.2-6.2; P = 0.02). Similar findings were seen when examining patients with versus without sinonasal disease and after removing relapses limited to the ear, nose, and throat., Conclusion: A patient-reported outcome measure of sinonasal disease, the SNOT-22, not only changes with disease activity in AAV, but also is associated with a higher risk of relapse within two years. These findings support the possibility that the SNOT-22 score may enhance prediction of relapse and that persistent sinonasal disease may be important in the pathophysiology of relapse., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease characterized by necrotizing inflammation of small blood vessels. Glucocorticoids (GC) in combination with rituximab or cyclophosphamide can reduce AAV-related mortality and rescue renal function. However, several side effects associated with these agents, including GC toxicity, are concerning. Avacopan, an inhibitor of the C5a receptor, is now available for AAV treatment and is expected to mitigate GC toxicity. We present a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis (MPA) with rapidly progressive glomerulonephritis treated with an early switch from GC to avacopan in combination with rituximab during induction therapy. Over a 6-month treatment period, clinical remission was achieved and maintained without infection or elevated liver enzyme levels. Efficacy and safety data regarding avacopan for AAV induction therapy remain limited. Therefore, more case reports are required to clarify the role of avacopan in AAV induction and maintenance therapy. Since the MPO-ANCA titer remained elevated despite the clinical remission of AAV in this case, the ANCA titer may not necessarily be a reliable biomarker for predicting AAV relapse when avacopan is applied as an induction therapy for AAV., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Systemic sclerosis (SSc) is a multi-system rheumatic disease characterized by vascular and fibrotic manifestations that can affect practically every organ. Scleroderma renal crisis (SRC) is the most common renal manifestation of SSc. However, with the use of angiotensin-converting enzyme inhibitors (ACEi), the morbidity and mortality associated with SRC has significantly reduced. Renal manifestations in SSc other than SRC have been generally under-recognized and can be left untreated, which can lead to grave consequences in this patient population. In this article, we will describe the spectrum of renal disease in SSc besides SRC., Materials and Methods: A literature search was conducted on PubMed and Cochrane from inception to December 2022 using medical subject headings (MeSH) terms for "scleroderma", "systemic sclerosis" combined with "renal injury", and "renal dysfunction". We included case reports, case series, observational studies, and literature reviews., Results: The initial search revealed 393 articles. After the exclusion of duplicates and non-relevant articles, data was included from 30 articles and 45 patients. The mean age was 55.2 years, 9 males (20%) and 36 females (80%). The most reported renal manifestations included: ANCA-associated vasculitis (n = 22), penicillamine-induced renal injury (n = 8), oxalate nephropathy (n = 5), Goodpasture syndrome (n = 4), nephrotic range proteinuria (n = 2), renal artery stenosis (n = 2), membranous glomerulonephritis (n = 1), and Evans syndrome (n = 1)., Conclusion: The spectrum of kidney involvement in SSc can range from asymptomatic reduction of the glomerular filtration rate to life-threatening scleroderma renal crisis. Therefore, it is essential that physicians closely monitor renal function in these patients for any emerging renal dysfunction.

The management of immune-mediated nephropathies in the elderly presents unique challenges due to age-related physiological changes, comorbidities, and frailty. This review addresses the clinical workup, diagnostic evaluation, and treatment strategies for this rapidly growing patient population. We highlight the inadequacies of current classification systems and the lack of evidence-based guidelines tailored to individuals ≥75 years. The review discusses the specific considerations in diagnosing and treating common conditions such as minimal change disease, focal and segmental glomerulosclerosis, membranous nephropathy, ANCA-associated vasculitis, infection-related and post-infectious glomerulonephritis, and anti-GBM disease. Managing these diseases requires a nuanced approach due to age-related changes in the immune system and the presence of multiple comorbidities. Immunosuppressive therapy, including corticosteroids, rituximab, and cyclophosphamide, remains a cornerstone of treatment, but the choice and dosage of drugs must be carefully balanced to avoid severe side effects. Comorbidity management, regular monitoring of kidney function, and a patient-centered approach are crucial for improving outcomes and quality of life. A multidisciplinary team can provide comprehensive care, addressing all aspects of the patient's health. Supportive care, the role of kidney biopsy, and the balance between immunosuppressive therapy and the risk of complications are emphasized. Collaborative, individualized care approaches are recommended to improve outcomes and quality of life for elderly patients with immune-mediated kidney diseases. Future research should focus on including older patients in clinical trials to establish robust, age-specific guidelines.

Objectives: Pneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors., Method: Data on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared., Results: Among 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD., Conclusions: MPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA. Key Points • Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients. • Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis. • In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA., (© 2024. The Author(s).)

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37 months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CT patterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present a case of a man in his 40s with pulmonary-renal syndrome due to myeloperoxidase-positive antineutrophil cytoplasmic antibodies-associated vasculitis and concurrent cold agglutinin disease, a combination that has not yet been described in the literature. The fulminant course of the disease, including the need for kidney replacement therapy and mechanical ventilation posed a significant treatment challenge due to haemolytic complications., Competing Interests: Competing interests: JL received consulting/lecture fees from Vifor Pharma., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma., Patient Concerns: A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain., Diagnoses and Interventions: Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient's performance status, we initiated low-dose steroid pulse therapy, followed by conservative management., Outcomes: While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis., Lessons: This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: To investigate whether circulating malondialdehyde (cMDA) at diagnosis could contribute to reflecting cross-sectional comprehensive inflammation or vasculitis activity and further predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 78 patients with AAV. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected as indices reflecting cross-sectional comprehensive inflammation, whereas the Birmingham vasculitis activity score (bVAS), and the five-factor score (FFS) were reviewed as AAV-specific indices. All-cause mortality was considered to be a poor outcome during follow-up. cMDA was measured from stored sera. Results: The median age of the 78 patients (32 men and 46 women) was 63.0 years. The median BVAS, FFS, ESR, and CRP were 5.0, 0, 24.5 mm/h, and 3.4 mg/L, respectively. Six patients died during the median follow-up duration based on all-cause mortality at 26.7 months. At diagnosis, cMDA was significantly correlated with cross-sectional ESR but not with BVAS or FFS. Compared to patients with cMDA < 221.7 ng/mL, those with cMDA ≥ 221.7 ng/mL at diagnosis exhibited an increased relative risk (RR 12.4) for all-cause mortality and further showed a decreased cumulative patient survival rate. Cox analyses revealed that cMDA ≥ 221.7 ng/mL (hazard ratio 24.076, p = 0.007) exhibited an independent association with all-cause mortality during follow-up in patients with AAV. Conclusions: cMDA at diagnosis may be a potential biomarker for predicting all-cause mortality during follow-up by reflecting comprehensive inflammation at diagnosis in patients with AAV.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease with limited data on outcomes after transplantation., Methods: In this single-center retrospective cohort study, we describe the outcomes of kidney transplant patients with AAV transplanted at our institute from February 2006 to January 2022., Results: We identified 9 patients among 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplantation was tacrolimus-based in 89% of the patients. At the end of a mean follow-up of 132 ± 61.1 months after transplantation, only one case of extrarenal vasculitis relapse was observed. The relapse rate was 0.01 per patient per year, which is comparable to that reported in the literature. However, seven patients were diagnosed with cancer after a mean follow-up of 81.4 months after transplantation; six had skin cancer and three had renal cell carcinoma (RCC) of the native kidneys (cumulative incidence of 78%). One patient died from metastatic squamous cell carcinoma., Conclusion: In this study, we found a noticeable decrease in disease relapse (1 relapse in the present cohort vs 7 relapses in 19 patients in the previous cohort) in kidney transplant patients with AAV compared with previous data from our group (December 1987-January 2006). Conversely, we found a high incidence of post-transplant cancer. This result could be attributed to reduced immunosurveillance due to immunosuppression therapy before and after transplantation. Therefore, constant cancer early diagnosis and prevention is mandatory during the post-transplant follow-up of AAV patients., (© 2024. The Author(s).)

Skeletal muscle involvement is common in patients with small- and medium-sized vasculitis, particularly polyarteritis nodosa (PAN) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Despite being not included in the standard classification criteria for PAN and AAV, skeletal muscle involvement is an important clinical indicator, particularly when vasculitic myopathy is the only pathological evidence in the absence of other organ involvement. Herein, we comprehensively reviewed and compared the clinical features of 71 and 135 patients with PAN and AAV, respectively, with skeletal muscle involvement at the time of disease onset. Most patients with PAN and AAV exhibited skeletal muscle involvement, often characterized by myalgia and occasional muscular weakness, predominantly in the lower extremities. Myalgia and weakness were observed more frequently in the distal lower extremities in patients with PAN than in those with AAV. In contrast, skeletal muscle involvement tended to exhibit a more dispersed distribution across all four extremities in those with AAV. Muscle magnetic resonance imaging T2-weighted and short-tau inversion recovery sequences can effectively identify hyperintense areas attributed to hypervascularity of affected muscle tissues and serve as a sensitive and useful modality for visually determining the suitable biopsy site. >90% of patients with PAN and AAV demonstrated perivascular inflammation in their affected muscle tissues, whereas fibrinoid necrosis of the vessel walls was reported in two-thirds of patients. Serum creatine kinase (CK) levels were within the normal range in approximately 80% of patients presenting with skeletal muscle involvement in PAN and AAV. Furthermore, muscle fiber damage was milder in patients with skeletal muscle involvement in PAN and AAV than those with idiopathic inflammatory myositis. Meanwhile, serum CK levels were elevated in 65-85% of patients with PAN and AAV who had myofiber necrosis and degeneration in the affected muscles. Most patients with PAN and AAV showed improvement in skeletal muscle involvement following glucocorticoids (GCs) administration; however, relapse was observed in some patients during the tapering of GCs. In summary, skeletal muscle involvement is a potential indicator for establishing PAN and AAV diagnoses during the early phases of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diseases of the nonneoplastic renal parenchyma occur in the context of a number of disorders that affect the organism systemically and can thus represent a differential diagnosis for autoimmunological kidney diseases., Purpose: Two common autoimmunologic diseases of the kidney, namely antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), are presented and put into context of the broader field of renal diseases. Novel diagnostic and therapeutic approaches are discussed., Materials and Methods: A review of the recent literature and an overview of the disease presentation are provided., (© 2024. The Author(s).)

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Methods: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed., Results: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively., Conclusions: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.

Objectives: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis., Methods: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models., Results: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001)., Conclusions: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Declaration of interests We declare no competing interests.

Intention: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment., Methods: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records., Results: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05)., Conclusion: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital., (© 2024. The Author(s).)

Objective: To quantify the magnitude of the risk of total and type-specific cardiovascular and cerebrovascular diseases (CCVD) in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)., Method: Searches of PubMed, Embase, and the Cochrane Library were conducted. Observational studies were included if they reported data on CCVD in AAV patients. Pooled risk ratios (RR) with 95% confidence intervals were calculated., Result: Fourteen studies met the inclusion criteria, comprising 20,096 AAV patients (over 46,495 person-years) with 5757 CCVD events. Compared with non-vasculitis population, AAV patients showed an 83% increased risk of incident CCVD (1.83 [1.37-2.45]; n = 10), 48% for coronary artery disease (1.48 [1.26-1.75]; n = 9), and 56% for cerebrovascular accident (1.56 [1.22-1.99]; n = 9). For type-specific CCVD, the risks of myocardial infarction, stroke, heart failure were increased by 67% (1.67 [1.29-2.15]; n = 6), 97% (1.97 [1.19-3.25]; n = 8) and 72% (1.72 [1.28-2.32]; n = 4), whereas there was only a trend toward a higher risk of angina pectoris (1.46 [0.90-2.39]; n = 2), and ischemic stroke (1.88 [0.86-4.12]; n = 4). Subgroup analyses by AAV type found significantly increased CCVD risk in both granulomatosis with polyangiitis (1.87 [1.29-2.73]; n = 7) and microscopic polyangiitis (2.93 [1.58-5.43]; n = 3). In three studies reporting impact of follow-up period after AAV diagnosis, the CCVD risk was significantly higher in the first two years after diagnosis than the subsequent follow-up (2.23 [2.00-2.48] vs. 1.48 [1.40-1.56]; p < 0.01). Significant heterogeneity existed in the main analyses., Conclusion: This meta-analysis demonstrates that AAV is associated with increased risks of overall and type-specific CCVD, especially within two years after AAV diagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD)., Methods: This is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed., Results: 39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases., Conclusion: Objective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: ANCA-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV., Methods: Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between 1 January 2000 and 31 December 2021 were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit., Results: The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA, and 13 had c-ANCA and/or PR3-ANCA. Mean (s.d.) age at AAV diagnosis was 63.4 (12.79) years; 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a 1-year timespan. Twenty-five (69%) patients had histopathological confirmation of AAV diagnosis in a location other than temporal artery, aorta or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36) and methotrexate (18/36) were the most frequent treatments., Conclusion: This is the largest single-centre cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV., Methods: Using a nested case-control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date., Results: A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48-3.75)] and 1.3% [HR 1.98 (95% CI 1.39-2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05-16.32)] and MACE [HR 5.78 (95% CI 2.67-12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA)., Conclusions: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Berden Classification and anti-neutrophil cytoplasmic antibody (ANCA) Renal Risk Score are classification models for rating renal histology and predicting outcome in patients with ANCA-associated Vasculitis/Glomerulonephritis (AAV/GN). In the present study we compare their ability to predict renal function outcome in short- and long-term follow up., Methods: Patients with an initial diagnosis of AAV/GN based on kidney biopsy were classified according to Berden and Renal Risk Score, started on the same treatment protocol, and were followed prospectively for up to 60 months. Renal function was recorded at 3mo(T3), 6mo(T6) and 60mo(T60), and results were compared to both classification systems., Results: Ninety four AAV/GN patients, M/F = 36/58, age = 60.05 (18-82)yrs were included. Based on Berden classification, patients grouped as Focal (n = 24), Crescentic (n = 35), Mixed (n = 21) and Sclerotic (n = 14), had significant differences in estimated glomerular filtration rate (eGFR) only at T3, while the percentage of those requiring hemodialysis differed at T0, T3, T6 but not at T60. According to the Renal Risk Score, patients were classified as Low (n = 8), Medium (n = 47) and High (n = 39) risk, and showed significant differences in both eGFR levels, proportion of hemodialysis, at T0, T3, T6 and end-stage kidney disease (ESKD) at T60. Even patients classified as Mixed (Berden) and as Medium or High risk (Renal Risk Score) had significant improvement from T0 to T6. Relapse could not be predicted by either system., Conclusion: Both methods were able to predict short-term renal function outcome and need for hemodialysis, but the Renal Risk Score showed significant superiority in predicting renal function outcome and ESKD after long-term follow up., (© 2024. The Author(s).)

Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic involvement and dialysis dependence are risk factors of infection., Objectives: To determine the prevalence of severe infection and associated factors in patients diagnosed with ANCA-associated vasculitis (AAV) and Polyarteritis Nodosa (PAN)., Methods: retrospective study was conduced in a single rheumatology center (2000-2018). We included patients diagnosed with AAV (Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (PAM) and Polyarteritis nodosa (PAN). Serious infectious events requiring hospitalisation or prolonged antibiotic/antiviral treatment, recurrent infection of Herpes Zoster Virus or opportunistic infections were evaluated. Sites of infection, isolated microorganisms and mortality related were analyzed., Results: 105 patients were analyzed, follow-up time median 18 m, 58.7% were women and median age was 52 years. Types of vasculitis: 41.9% PAM, 16.2% EPGA, 40% GPA, 1.9% PAN. Constitutional, pulmonary, renal and otorhinolaryngology manifestations were the most frequent., Prevalence of Infection: 34.2%, with a median of 3 months from diagnosis of vasculitis to the infectious event. Low respiratory tract (42.8%), sepsis (31.4%), and urinary tract (14.3%) were the most common sites of infections. Bacterial aetiology was the most prevalent (67.7%). Mortality at the first event was 14.3% and a 72.2% of patients were in the induction phase of treatment. Infectious events were significantly associated with age > 65 years (p = 0.030), presence of lung (p = 0.016) and renal involvement (p = 0.001), BVASv3 > 15, mortality (p = 0.0002)., Conclusions: The prevalence of infection was 34.2%. Lower airway infections, septicemia and urinary tract infections were the most prevalent. Infections were associated with renal and pulmonary involvement, age older than 65 years and score BVAS > 15. Severe infections were associated with mortality, especially in elderly patients., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results: At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH ( n  = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21-1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22-26 vs. 22-27) and fewer with reduced GC (median, 23; IQR, 20-25) versus standard GC (median, 26; IQR, 25-28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions: Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).

Background: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children., Methods: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored., Results: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation., Conclusions: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB)., (© 2023. The Author(s).)

Background/aims: This study applied the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with systemic sclerosis (SSc) and investigated the frequency of overlap syndrome of SSc and AAV (SSc-AAV-OS)., Methods: Among the 232 patients diagnosed with SSc, 105 with signs suggestive of small- or medium-vessel vasculitis, which were defined as the present of interstitial lung disease (ILD), peripheral neuropathy, or suspected renal vasculitis, were included in this study and analyzed., Results: Among the 105 SSc patients, the detection rate of ANCA was 19.0%. When the 2022 ACR/EULAR criteria were applied, the frequency of SSc-AAV-OS was 20.0%, which was much higher than 1.7% reported with previous criteria for AAV. ANCA positivity contributed to the reclassification of SSc-AAV-OS more than ANCA negativity in SSc patients with signs suggestive of small- or medium-vessel vasculitis., Conclusion: The frequency of SSc-AAV-OS in SSc patients with signs suggestive of small- or medium-vessel vasculitis at diagnosis was 20.0%. Therefore, we suggest that physicians should perform ANCA tests in SSc patients exhibiting signs suggestive of small- or medium-vessel vasculitis and apply the new criteria for AAV.