Glucocorticoid Minimization in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An International Survey of Clinicians.

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.

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.

Cardiovascular and cerebrovascular outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis: A systematic review with meta-analysis.

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.

A case of ANCA-negative pauci-immune crescentic glomerulonephritis with lung adenocarcinoma with mediastinal involvement successfully treated by corticosteroid and radiation therapy.

Pauci-immune crescentic glomerulonephritis (PICGN) is one of the pathologies causing rapidly progressive glomerulonephritis, often associated with anti-neutrophil cytoplasmic antibody (ANCA); however, in 10-30% of cases, ANCAs are negative. While a relatively large number of cases of ANCA-positive PICGN complicated with malignancy have been previously reported, the number of cases of ANCA-negative PICGN with malignancy is limited. The prognosis for such cases was poor, and many patients died within a relatively short period. Here, we report the case of ANCA-negative PICGN complicated with malignancy successfully treated by corticosteroid and radiation therapy. A 63-year-old Japanese man was admitted to our hospital due to spiking fevers in the previous 3 months. Based on the findings of imaging and pathological tests, he was diagnosed with locally advanced lung adenocarcinoma with mediastinal involvement. After admission, his renal function rapidly deteriorated, and urinalysis showed heavy proteinuria. In serological tests, serology for autoantibodies, including ANCAs, was negative. The kidney biopsy revealed PICGN with prominent endocapillary proliferation. We administered corticosteroid therapy for glomerulonephritis and subsequent radiation therapy for lung carcinoma, both of which were effective. He has been alive without progression of malignancy or kidney disease for 5 years after discharge. In patients with malignancy presenting with acute deterioration of kidney function, although infrequent, one of the conceivable pathological conditions to consider is ANCA-negative PICGN associated with malignancy. In such cases, even with negative antibodies such as ANCA, pathological examination is warranted, and a combination of anti-tumor therapy and immunosuppressive therapy is expected to be effective.

[Clinical characteristics of children with anti-neutrophil cytoplasmic antibody-associated vasculitis]. / å„¿ç«¥æŠ—ä¸­æ€§ç²’ç»†èƒžèƒžè´¨æŠ—ä½“ç›¸å ³æ€§è¡€ç®¡ç‚Žä¸´åºŠç‰¹å¾åˆ†æž.

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.

Clinical characteristics and outcome of double-seropositive patients with anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies.

OBJECTIVE: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. RESULTS: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) µmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 µmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. CONCLUSIONS: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.

Sterile Endocarditis and Splenic Infarct: A Rare Masquerading Presentation of Granulomatosis With Polyangiitis in a Patient With Pulmonary Aspergillosis.

Granulomatosis with polyangiitis (GPA) is a rare multisystem disease characterized by vasculitis affecting small vessels, resulting in the formation of necrotising granulomata, primarily affecting the lungs, the upper respiratory tract, and kidneys. Almost all patients have upper and lower respiratory involvement; up to 85% of patients with GPA develop kidney disease within two years of diagnosis. Cutaneous, neurological, and ocular manifestations are also seen with varying frequencies. However, cardiac manifestations of the disease are rare and scarcely reported in the literature. Here, we report a case of a 65-year-old female with an initial diagnosis of pulmonary aspergillosis based on the presence of septate hyphae branching at acute angles on lung biopsy and elevated serum galactomannan, who, over the following months, developed a multitude of issues such as myocardial infarction, sterile endocarditis, splenic infarction, and heart block, as well as the challenges faced in establishing a diagnosis and managing its complications.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

Progression to ANCA-associated vasculitis in patients with idiopathic interstitial pneumonia and positive ANCA.

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.

Use of mesna prophylaxis in patients with cyclophosphamide-treated ANCA-associated vasculitis: cross-sectional survey of practitioners.

BACKGROUND: There may be some diversity in the practice of co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV). OBJECTIVES: To assess the practice of prescribing mesna prophylaxis for CYC-treated patients with AAV. METHODS: We invited authors of publications on AAV referenced in MEDLINE over the previous 10 years to participate in an anonymous online survey. Respondents were eligible if they were involved in CYC treatments for AAV. The survey asked about the characteristics of the respondents and their practice in using CYC and mesna to treat AAV and the underlying rationale. We compared 18 variables between mesna prescribers and their counterparts to identify factors associated with mesna use. RESULTS: In total, 139 eligible individuals completed the survey. The participants were from 34 countries and were essentially physicians (98%). Overall, 68%, 19% and 13% of respondents prescribed mesna systematically, never, or on a selective basis. As compared with never/selective-prescribers, systematic-prescribers were more often ≤ 39 years old (P = 0.008), more often used intermittent pulse therapy as the exclusive/predominant CYC administration scheme (P < 0.001), were more frequently based in France/Germany/Italy than in England/United States (P < 0.001), and more often indicated adherence to local standards (P = 0.003) or (inter)national guidelines for AAV (P < 0.001) as a rationale for their mesna practice. Never/selective-prescribers more commonly reported that their mesna prescription pattern had changed as compared with their former practice (P < 0.001). CONCLUSIONS: Systematic co-prescription of mesna is the prevailing practice for CYC treatments for AAV. The practice seems to involve practicability considerations and differs between generations.

Exploration of the Shared Gene Signatures and Molecular Mechanisms between Chronic Bronchitis and Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis: Evidence from Transcriptome Data.

BACKGROUND: Chronic Bronchitis (CB) is a recurrent and persistent pulmonary inflammation disease. Growing evidence suggests an association between CB and Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis (ANCA-GN). However, the precise mechanisms underlying their association remain unclear. AIMS: The purpose of this study was to further explore the molecular mechanism of the occurrence of chronic bronchitis (CB) associated with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). OBJECTIVE: Our study aimed to investigate the potential shared pathogenesis of CB-associated ANCA-GN. METHODS: Datasets of ANCA (GSE108113 and GSE104948) and CB (GSE151052 and GSE162635) were obtained from the Gene Expression Omnibus (GEO) datasets. Firstly, GSE108113 and GSE151052 were analyzed to identify common differentially expressed genes (DEGs) by Limma package. Based on common DEGs, protein-protein interaction (PPI) network and functional enrichment analyses, including GO, KEGG, and GSEA, were performed. Then, hub genes were identified by degree algorithm and validated in GSE104948 and GSE162635. Further PPI network and functional enrichment analyses were performed on hub genes. Additionally, a competitive ceRNA network was constructed through miRanda and spongeScan. Transcription factors (TFs) were predicted and verified using the TRRUST database. Furthermore, the CIBERSORT algorithm was employed to explore immune cell infiltration. The Drug Gene Interaction Database (DGIDB) was utilized to predict small-molecular compounds of CB and ANCA-GN. RESULTS: A total of 963 DEGs were identified in the integrated CB dataset, and 610 DEGs were identified in the integrated ANCA-GN dataset. Totally, we identified 22 common DEGs, of which 10 hub genes (LYZ, IRF1, PIK3CG, IL2RG, NT5E, ARG2, HBEGF, NFATC2, ALPL, and FKBP5) were primarily involved in inflammation and immune responses. Focusing on hub genes, we constructed a ceRNA network composed of 323 miRNAs and 348 lncRNAs. Additionally, five TFs (SP1, RELA, NFKB1, HIF1A, and SP3) were identified to regulate the hub genes. Furthermore, immune cell infiltration results revealed immunoregulation in CB and ANCA-GN. Finally, some small-molecular compounds (Daclizumab, Aldesleukin, and NT5E) were predicted to predominantly regulate inflammation and immunity, especially IL-2. CONCLUSION: Our study explores the inflammatory-immune pathways underlying CB-associated ANCA-GN and emphasizes the importance of NETs and lymphocyte differentiation, providing novel insights into the shared pathogenesis and therapeutic targets.

Propylthiouracil-Induced Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Presenting with Multiple Sterile Abscesses, Mononeuritis Multiplex, and Splenic Vein Thrombosis: A Case Report and Literature Review.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) represents a rare group of disorders, that traditionally includes diseases like granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). However, AAV can also be triggered by medications such as propylthiouracil (PTU). This article focuses on the subset of drug-induced AAV. We examine how certain medications, notably PTU, can provoke an AAV response, detailing the pathophysiological mechanisms and clinical implications. A 72-year-old female being treated with PTU presented with bilateral hand abscesses, generalized weakness, and frequent falls. Despite initial treatments, her condition worsened, prompting consideration of AAV secondary to PTU. Following appropriate diagnostic procedures and initiation of treatment, including steroids, heparin, and rituximab, the patient showed significant improvement. PTU-induced AAV is a serious, albeit rare, side effect characterized by anti-neutrophil cytoplasmic autoantibodies, with the potential for varied organ involvement and generally a better prognosis than primary AAV. The atypical presentation in this case underscores the importance of clinician vigilance and awareness, ensuring timely diagnosis and appropriate management of this complex condition.

Accelerated atherosclerosis in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: case report.

Accelerated atherosclerosis has been identified as a complication of multiple autoimmune diseases, among which Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis stands out. We describe the case of a 60-year-old patient with a history of hypertension, diabetes mellitus, and chronic kidney disease of unknown etiology, who presented two acute coronary syndromes with only a six-month difference. Rapid progression of coronary involvement was evidenced, along with increased markers of inflammatory response, usual interstitial pneumonia on tomography, and positive anti-myeloperoxidase antibodies (anti-MPO), leading to the diagnosis of microscopic polyangiitis (MPA). In these cases, timely diagnostic suspicion is crucial, as early treatment significantly impacts the course and prognosis of the disease.

A case of rapid avacopan-induced liver injury in pediatric granulomatosis with polyangiitis.

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered.

Sinonasal manifestations of granulomatosis with polyangiitis: A retrospective analysis.

OBJECTIVE: This study aimed to examine the characteristics of nasal and imaging findings of sinonasal lesions in granulomatosis with polyangiitis (GPA) patients and how these lesions change over time in both the active and remission phases of the disease. METHODS: We retrospectively reviewed GPA patients with sinonasal lesions who were followed up at our department between January 2005 and December 2020. The following data were collected: age, sex, symptoms at initial presentation, anti-neutrophil cytoplasmic antibody (ANCA) type, and histopathological, nasal (initial and follow-up), and imaging (initial and follow-up) findings. RESULTS: This study included 17 patients with GPA aged 30 to 79 years. Computed tomography (CT) of the sinuses showed mucosal thickening in 16 patients, bone thickening in 12, bone destruction in 4, and an orbital invasion mass in 3 at the time of diagnosis. After initiating treatment, mucosal thickening of the sinuses improved in 3 of 16 patients and remained unchanged in 13. Bone thickening at the time of diagnosis remained unchanged in 10 of 12 patients and worsened in 2; 1 patient displayed newly developed bone thickening. Destructive nasal findings on CT were positive for proteinase 3-ANCA. CONCLUSIONS: Our study revealed that mucosal thickening, bone thickening, bone destruction, and orbital invasion mass were major CT findings in patients with GPA. Intranasal findings such as granulations, crusting, and necrosis were seen in the active phase; moreover, saddle nose, loss of turbinate, and nasal septal perforation were subsequently seen in the course of the disease. Sinonasal findings of GPA vary depending on the disease stage and period.

Diagnostic delays in systemic vasculitides.

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.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD).

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.

[Clinical analysis of ear symptoms of 40 patients with ANCA-associated vasculitis].

Objective:To analyze the clinical feature, diagnosis and treatment of Anca-associated vasculitis with ear symptoms. Methods:In this retrospective study, we summarized the clinical and laboratory examination, pure tone audiometry, aural immittance measurement, CT scan of temporal bone and treatment of 40 patients in the First Medical Center of the PLA General Hospital. Results:A total of 11 cases（27.5%） had the initial symptom in the ear. The most common symptoms were hearing loss, and the other symptoms included a sense of ear fullness, otorrhea and tinnitus. There were 35 cases with hearing loss: 19 cases with conductive hearing loss（47.5%）, 9 cases with sensorineural hearing loss（22.5%）, and 7 cases with mixed hearing loss（17.5%）. 5 cases had a sense of ear fullness or tinnitus, and the results of the hearing test were normal（12.5%）. All of the 40 patients had multi-system involvement, and respiratory system accounted for the most. All patients had a positive result of Anti-neutrophil cytoplasmic antibody（ANCA）. Treatment included systemic hormonal, immunosuppressive, or biologic therapy. There were 3 cases recovered（7.5%）, 22 cases with alleviated ear symptoms（55.0%）, 6 cases with recurrent hearing loss（15%） and 9 cases had no significant improvement（22.5%）. Conclusion:Conductive deafness（secretory otitis media） can be the first manifestation in the early stage of otitis media with AAV（OMAAV）, later it may turn to binaural mixed deafness. Otolaryngologists need to consider OMAAV diagnosis when diagnosing and treating patients with recurrent secretory otitis media. Multi-system symptom consultation and ANCA examination can help identify. Early systemic medication and the application of immunosuppressants or biological agents can help relieve the ear symptoms.

Protective effect of astaxanthin on ANCA-associated vasculitis.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-α in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-α, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-α. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-α were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid.