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Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a rare autoimmune disease which is managed by a range of specialities. There are limited data on treatment practices in Australia and New Zealand. Aims: To understand current patterns of acute AAV treatment in Australia and New Zealand. Methods: An online survey was conducted between July and October 2022 investigating physicians' views on the management of AAV, focusing on induction therapy. The survey contained questions pertaining to access to treatment and responses to clinical management scenarios. Eosinophilic granulomatosis with polyangiitis was not included. A chi‐squared test of independence was performed for statistical analysis. Results: From a total of 55 responses, plasma exchange was difficult to access for 44% of respondents, more so in rural centres, and they also had difficulty accessing infusion centres. New Zealand clinicians had more difficulty accessing rituximab, with only 44% reporting easy access compared with Australian clinicians (93%). With clinical management scenarios, there was variation in the dosing regimen of glucocorticoids and initiation of plasma exchange, with 42% of respondents prescribing a glucocorticoid regimen different from the standard of care, the 'reduced‐dose' arm of the Plasma Exchange and Glucocorticoids for the Treatment of ANCA‐Associated Vasculitis trial. The choice of cyclophosphamide or rituximab for induction therapy was based on patient characteristics and medical history. Conclusions: There is substantial variation in approaches to the acute management of AAV in Australia and New Zealand, including differences in resource availability. This variation in care demonstrates the need to implement current practice guidelines and institute contemporary monitoring of AAV management, to achieve best patient outcomes. [ABSTRACT FROM AUTHOR]

Systemic vasculitides are among the less common disorders encountered in routine rheumatology practice. The low incidence and heterogeneous presentation at onset can potentially lead to delayed diagnosis. Not recognizing these in the early phase may prove detrimental, as some vasculitis may progress to a catastrophic course with major morbidity or mortality. The causes of diagnostic delay may vary among different types of vasculitis and may also be disease-, patient-, or physician-related. Disease-related factors include the myriad presentations with diverse and non-specific symptoms, mimicking other conditions like infections. In addition, some forms have prolonged prodromal phases before evident organ damage. Limited awareness among healthcare professionals, particularly outside rheumatology, and a lack of readily available diagnostic tools contribute to missed diagnoses. Delays in seeking care due to non-specific symptoms or lack of access to specialist care can worsen outcomes. The economic burden also increases with delayed diagnosis and damage accrual when the disease remains unrecognized or untreated for prolonged periods. Although the causes of vasculitis are numerous, including secondary causes, in this review, we focus on diagnostic delays in primary vasculitides and suggest potential steps to identify and treat these diseases early. These include educating both healthcare professionals and the public about the signs and symptoms of vasculitis; expanding the rheumatology workforce and facilitating timely referrals; implementing readily available and reliable tests for early detection; and streamlining care and diagnostic pathways. Such measures have the potential to improve the overall outcomes of the disease, with prolonged remission, minimal damage accrual, and improved quality of life. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T-cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents the case study of 64-year- old male with a nearly 40-year history of migraine (2–6 attacks/month) with recurrent headaches, fever, and neurological symptoms. Topics include the patient's history of recurrent headaches, fever, numbness in the left limb, and persistent headache, as well as the diagnostic process and treatment.

Background: The epidemiology of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) varies worldwide. Previous Australian studies described a higher incidence of AAV in rural areas; however, this has not yet been investigated in Victoria. Aims: To calculate the incidence of AAV in rural and regional Victoria and characterise the demographics and clinical outcomes of this cohort. Methods: We performed a retrospective review of patients with newly diagnosed AAV confirmed on renal biopsy at Bendigo Health between 2013 and 2021. Cases were classified according to the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. Local disease incidence was calculated using Estimated Resident Population data for our catchment, the Loddon Mallee region. Results: Twenty‐eight cases of new AAV were identified; 17 were classified as microscopic polyangiitis (MPA) and the remainder as granulomatosis with polyangiitis (GPA). The median age at diagnosis was 68 years (interquartile range (IQR): 59–77). The incidence per million person‐years was 9.3 for AAV overall (95% CI: 6.2–13.5), 5.7 for MPA (95% CI: 3.3–9.1) and 3.7 for GPA (95% CI: 1.8–6.6). With a median follow‐up time of 3.3 years (IQR: 1.9–5.6), one‐quarter of patients relapsed (n = 7, 25%), and six required ongoing renal‐replacement therapy (21%). Conclusions: The calculated incidence of AAV in rural and regional Victoria is not higher than the reported incidence in most urban Australian cohorts. This study may underestimate the true local disease incidence as only patients with renal vasculitis were included. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries, and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians should accept as the lowest glucocorticoid dosing that can be used in induction therapy for AAV. Study Design: International, online survey. Setting & Participants: Clinicians in various countries with experience in managing vasculitis. Exposure and Outcomes: Survey questions to gauge interest and preferences in studying an induction of remission regimen for severe AAV using only 2 or 4 weeks of glucocorticoids without avacopan. Data collected included general opinions about standard of care for induction agents, glucocorticoids, and avacopan. Respondents were presented with 3 candidate trial designs, 2 of which proposed a combination of cyclophosphamide and rituximab induction. Analytical Approach: Using a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen would be safe and effective and their willingness to randomize into the trial. Results: There were 210 respondents to the survey. The candidate trials were rated moderate-to-high for usefulness to demonstrate safety and efficacy (scores 6-7/10), and moderate (scores 5-6/10) for willingness to randomize. Four-week glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4-week glucocorticoids was the most preferred design. Forty-two percent of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients. Limitations: Representativeness of survey sample and generalizability of findings. Conclusions: Combination cyclophosphamide-rituximab may be the ideal way of studying minimal glucocorticoid use in severe AAV. Given its increasing uptake, incorporating avacopan into a potential trial design is important. Plain Language Summary: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on using less glucocorticoids to limit side effects. New drugs that drastically limit glucocorticoid use are not available in many countries. Studies are needed to find other ways of reducing glucocorticoid exposure to treat AAV, but it is unclear how best to achieve this. We administered a survey to doctors with experience in treating AAV and had them grade different combinations of widely available treatments with 2 or 4 weeks of glucocorticoids. We found that a combination of 2 doses cyclophosphamide with 2 doses rituximab and 4 weeks of glucocorticoids was the preferred treatment. The results will guide the development of a trial studying minimal use of glucocorticoids for the treatment of AAV.

OBJECTIVE: To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis. METHODS: Patients with GCA, Takayasus arteritis (TAK), PAN and the three forms of ANCA-associated vasculitis [AAV; granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)] enrolled in a prospective, multicentre, longitudinal study were included. RESULTS: The study included data on 2085 patients [63% female, 90% White] with a mean age of 54.6 years (s.d. 17.2). Diagnoses were GCA (20%), TAK (11%), PAN (5%), GPA (42%), microscopic polyangiitis (8%) and EGPA (14%). Hypothyroidism was present in 217 patients (10%) (83% female), with a mean age 59.8 years (s.d. 14.5). Age- and sex-adjusted risk of hypothyroidism was GCA, odds ratio (OR) 0.61 (95% CI 0.41, 0.90); TAK, OR 0.57 (95% CI 0.31, 1.03); PAN, OR 0.59 (95% CI 0.25, 1.38); GPA, OR 1.51 (95% CI 1.12, 2.05); microscopic polyangiitis, OR 1.81 (95% CI 1.18, 2.80) and EGPA, OR 0.82 (95% CI 0.52, 1.30). Among patients with AAV, age- and sex-adjusted risk of hypothyroidism was higher with positive MPO-ANCA [OR 1.89 (95% CI 1.39, 2.76)]. The clinical manifestations of vasculitis were similar in patients with and without hypothyroidism, except transient ischaemic attacks, which were more frequently observed in patients with GCA and hypothyroidism (12% vs 2%; P = 0.001). CONCLUSIONS: Differences in the risk of hypothyroidism among vasculitides may be due to genetic susceptibilities or immune responses. This study confirms an association of hypothyroidism with MPO-ANCA.

Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury—serum sulfatides, soluble thrombomodulin, and pentraxin 3—serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are systemic necrotizing vasculitides associated with significant morbidity and mortality. Given the immunosuppression used to manage these conditions, it is important for clinicians to recognize complications, especially infectious ones, which may arise during treatment. Kaposi sarcoma (KS) is a lymphoangioproliferative neoplasm caused by human herpes virus 8 (HHV-8). Its cutaneous manifestations can mimic vasculitis. We describe a 77-year-old man with microscopic polyangiitis with pulmonary-renal syndrome treated with prednisone and intravenous cyclophosphamide who developed KS (HHV-8 positive) after 2 months of treatment. Cyclophosphamide was discontinued and prednisone gradually lowered with improvement and clinical stabilization of KS lesions. This comprehensive review includes all published cases of KS in patients with AAV, with a goal to summarize potential risk factors including the clinical characteristics of vasculitis, treatment and outcomes of patients with this rare complication of immunosuppressive therapy. We also expanded our literature review to KS in other forms of systemic vasculitis. Our case-based review emphasizes the importance of considering infectious complications of immunosuppressive therapy, especially glucocorticoids, and highlights the rare association of KS in systemic vasculitis.

Anti-neutrophil cytoplasmic antibody-associated vasculitis is triggered by infection, dust exposure, and drugs. A 73-year-old male presented with dyspnea. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was confirmed upon admission. Exacerbation of interstitial pneumonia and renal dysfunction were observed. Analysis revealed positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibody, other anti-aminoacyl transfer RNA synthetase antibodies, and anti-melanoma differentiation-associated gene 5. Renal biopsy confirmed crescentic glomerulonephritis, leading to the diagnosis of microscopic polyangiitis. Combination therapy with prednisolone and cyclophosphamide was initiated, resulting in improved respiratory and renal failure. There is a potential association between SARS-CoV-2 infection and the onset of autoimmune diseases.

Objective To investigate the CT features and clinical characteristics of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in different target antigen types. Methods 209 patients with clinically confirmed pulmonary AAV in our hospital between January 2012 and July 2022 were divided into 188 myeloperoxidase-ANCA (MPO-ANCA)-positive and 21 proteinase 3-ANCA (PR3-ANCA)-positive groups according to the different specificity of the target antigens. The chest CT features and clinical characteristics of the two groups were retrospectively compared. Results AAV involved the kidneys (187), respiratory tract (82), joints (8), digestive system (7), skin (7), hematological system (5), paranasal sinuses, ears, and eyes (5). The CT appearance included ground glass opacities (186), fibrous striae (110), pulmonary maculopathy/emphysema (103), reticular opacities (96). pleural effusion (94), bronchiectasis (81), consolidations (68), pericardial effusion (67), nodule/mass (57), and honeycombing (55). The proportion of PR3-ANCA-positive patients present with hematochezia, arthralgia, and skin rash, and proportion of nodules/masses on chest CT were both significantly higher than that of MPO-ANCA-positive patients (P<0.05). MPO-ANCA- positive patients had significantly higher rates of ground glass opacities, reticular opacities, honeycombing, bronchiectasis, and pulmonary maculopathy/emphysema than that of PR3-ANCA-positive patients (P<0.05). Conclusion Chest CT appearance and clinical characteristics differ between target antigen types of AAV. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin G (IgG) contains a conserved N-glycan in the fragment crystallizable (Fc), modulating its structure and effector functions. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) alterations of IgG Fc-glycosylation have been observed to correlate with the disease course. Here, we examined longitudinal changes in N-linked Fc glycans of IgG in an AAV patient cohort and their relationship with disease flares. Methods: Using liquid chromatography coupled with mass spectrometry, we analysed IgG Fc-glycosylation in 410 longitudinal samples from 96 individuals with AAV. Results: Analysis of the cross-sectional differences as well as longitudinal changes demonstrated that IgGs of relapsing PR3-ANCA patients have higher Fc-bisection at diagnosis (P= 0.004) and exhibit a decrease in Fc-sialylation prior to the relapse (P= 0.0004), discriminating them from non-relapsing patients. Most importantly, PR3-ANCA patients who experienced an ANCA rise and relapsed shortly thereafter, exhibit lower IgG Fc-fucosylation levels compared to non-relapsing patients already 9 months before relapse (P= 0.02). Discussion: Our data indicate that IgG Fc-bisection correlates with long-term treatment outcome, while lower IgG Fc-fucosylation and sialylation associate with impending relapse. Overall, our study replicated the previously published reduction in total IgG Fc-sialylation at the time of relapse, but showed additionally that its onset precedes relapse. Furthermore, our findings on IgG fucosylation and bisection are entirely new. All these IgG Fc-glycosylation features may have the potential to predict a relapse either independently or in combination with known risk factors, such as a rise in ANCA titre. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD than in those without ESRD (p = 0.009). Multivariate analyses revealed that high serum creatinine levels (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.25–15.5) and high serum C4 levels (OR 1.24, 95% CI 1.03–1.49) were risk factors for ESRD. Using receiver operating characteristic analysis, the cut-off value for initial serum C4 levels and serum creatinine levels were 29.6 mg/dL and 3.54 mg/dL, respectively. Patients with MPA with a greater number of risk factors (serum C4 levels > 29.6 mg/dL and serum creatinine levels > 3.54 mg/dL) had a higher ESRD progression rate. Serum C4 levels were significantly positively correlated with serum creatinine levels and kidney Birmingham vasculitis activity score (p = 0.02 and 0.04, respectively). These results suggest that serum C4 levels are useful tools for assessing renal disease activity and prognosis in MPA. [ABSTRACT FROM AUTHOR]

We report a rare case of severe exudative retinal detachment with orbital granuloma associated with granulomatosis with polyangiitis (GPA). A 42-year-old man developed bilateral conjunctival hyperemia and eye pain 15 months before presenting to us. Because vitreous cells and retinal detachment were detected in his left eye, he was referred to us for further evaluation. The left eye showed scleral edema, cells in the anterior chamber and anterior vitreous, exudative retinal detachment, and elevated white subretinal lesions from the nasal to the inferior parts of the eye fundus. Orbital contrast-enhanced magnetic resonance imaging revealed a granulomatous lesion, retinal detachment, and fluid retention in the left eyeball. Comprehensive rheumatological evaluation revealed proteinase 3 anti-neutrophil cytoplasmic antibody positivity and a history of otitis media, leading to a GPA diagnosis. Methylprednisolone 1,000 mg/day was administered intravenously for 3 days, followed by oral prednisolone and intravenous cyclophosphamide. Although the retinal detachment decreased, scleritis and choroidal detachment relapse were observed in the left eye after the fifth cyclophosphamide administration. After switching from cyclophosphamide to rituximab, the scleritis and choroidal detachment resolved. Remission was successfully maintained with biannual rituximab administration. In this case, we conclude that rituximab was important to re-induce and maintain remission after recurrence. Collaboration with a rheumatologist is essential for proper treatment in related cases. This is the first report of ultra-widefield and multimodal imaging for retinal detachment associated with GPA.