Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging.In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy.Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

BACKGROUND: 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.
METHODS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease categorized as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The majority of patients are ANCA-positive, predominantly against myeloperoxidase (MPO). Previous studies have predominantly concentrated on the association between EGPA and neutrophils, but recent research has emphasized the role of lymphocytes in the development of EGPA. The objective of our research was to examine the causal association between immune cells and MPO + ANCA EGPA. A two-sample bidirectional Mendelian randomization (MR) analysis was performed, which included 159 MPO + ANCA EGPA cases and 6688 controls and utilized Genome-Wind Associaton Studies (GWAS) summary statistics of immune traits from approximately 3757 individuals, encompassing around 22 million single nucleotide polymorphisms (SNPs). Our findings revealed that 23 immunophenotypes were associated with MPO + ANCA EGPA. Furthermore, the reverse MR analysis showed that MPO + ANCA EGPA had significant causal effects on three immunophenotypes within the Treg panel. By integrating existing research, our study unveiled the contributions of Tregs, B cells, and monocytes to the development of EGPA. Subgroup analysis specifically examined the roles of lymphocyte subtypes, cytokines, and their surface molecules in the pathogenic mechanisms of the disease. This comprehensive approach provides a novel perspective on the biological mechanisms and early intervention strategies for MPO + ANCA EGPA by focusing on immune cells.

ANCA-associated vasculitis brings together three diseases, granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. This group of diseases has benefited over the last 3 decades from major therapeutic advances both in terms of therapeutic strategies and availability of new drugs, mainly for targeted therapies. Treatments, whether conventional or not, include an induction phase followed by a maintenance phase. Induction treatment today poses few problems. It is essentially based on the combination of corticosteroids and rituximab or cyclophosphamide. Remission is achieved in less than 6 months and maintenance treatment, preventing relapses, is then started. We showed that the best maintenance treatment was rituximab, surpassing the efficacy of methotrexate or azathioprine. During this phase, corticosteroid therapy is stopped or given at a very small dose. In Eosinophilic Granulomatosis with Polyangiitis (GEPA), the strategy is slightly different and there is a lack of prospective trials to demonstrate the benefits of rituximab or mepolizumab (anti-IL5) in inducing remission. Regarding maintenance treatment, prolonged corticosteroid therapy (orally and/or inhaled) is often necessary to control asthmatic disease. Only mepolizumab has shown its ability to prevent relapses and reduce the dose of corticosteroids controlling asthma. The current questions posed by maintenance treatment are its duration which could be variable and adapted to the risk of relapse and the risks induced by prolonged immunosuppression, particularly infectious.
UNASSIGNED: Vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) : actualités thérapeutiques.
UNASSIGNED: Les vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) réunissent trois maladies, la granulomatose avec polyangéite, la polyangéite microscopique et la granulomatose éosinophilique avec polyangéite. Ce groupe de maladies a bénéficié au cours des trois dernières décennies d’avancées thérapeutiques majeures tant en termes de stratégies thérapeutiques que de mise à disposition de nouveaux médicaments, essentiellement pour des thérapies ciblées. Les traitements, conventionnels ou non, comprennent une phase d’induction suivie d’une phase d’entretien. Le traitement d’induction pose aujourd’hui peu de problèmes. Il est essentiellement fondé sur l’association corticoïdes et rituximab ou cyclophosphamide. La rémission est obtenue en moins de 6 mois et un traitement d’entretien, préventif des rechutes, est alors initié. Nous avons montré que le meilleur traitement d’entretien était le rituximab, surpassant l’effet du méthotrexate ou de l’azathioprine. Durant cette phase, la corticothérapie est arrêtée ou donnée à très petite dose. Dans la granulomatose éosinophilique avec polyangéite (GEPA), la stratégie est un peu différente et les essais prospectifs manquent pour démontrer l’intérêt du rituximab ou du mépolizumab (anti-IL5) en induction de la rémission. En traitement d’entretien, une corticothérapie prolongée (par voie orale et/ou inhalée) est souvent nécessaire pour contrôler la maladie asthmatique. Seul le mépolizumab a montré sa capacité à prévenir les rechutes et à réduire la dose de corticoïdes contrôlant l’asthme. Les questions actuelles que pose le traitement d’entretien sont notamment sa durée qui pourrait être variable et adaptée au risque de rechute et les risques induits par l’immunodépression prolongée, notamment infectieux.

Objective: This paper aimed to describe another form of aggressive limited Granulomatosis with polyangiitis (GPA) revealed by dacryoadenitis. Methods and results: We report an unusually limited GPA in a 48-year-old man presenting with bilateral proptosis. She had never presented kidney or pulmonary manifestations, but her disease was persistently active including oto-rhino-laryngological manifestations, dacryoadenitis, and neurological manifestations unresponsive to corticosteroids and immunosuppressors. Discussion: Granulomatosis with polyangiitis (GPA) is an auto-immune inflammatory vasculitis. Involvement of lacrimal glands as the first presentation is uncommon. It is characterized by the development of granulomas. Patients with orbital mass without lacrimal gland involvement have a higher rate of systemic disease, a severe clinical course, and a higher rate of recurrences. A patient with dacryoadenitis seems to be with a good prognosis. Eye manifestations were significantly more common in patients with pachymeningitis. MPO-ANCA-positive pachymeningitis was more frequent in older female patients. PR3-ANCA-positive pachymeningitis had more severe neurological damage. Induction treatment consists of intravenous methylprednisolone (IV) associated with cyclophosphamide. Conclusion: Faced with dacryoadenitis, it is important to screen for ANCA-associated vasculitis. Abbreviations: GPA = Granulomatosis with polyangiitis, ANCA = Antineutrophil Cytoplasmic Antibodies.

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OBJECTIVE: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is often organ- or life-threatening in children and impacts them during important periods of psychosocial and physical development. This review covers recent advances in the pathophysiology, diagnosis, management, and outcomes of AAV in children and highlights the ongoing need for funding and increased research collaboration.
RESULTS: Recent work has improved our understanding of AAV disease pathogenesis, potentially identifying new biomarkers and therapeutic targets. Collaborative clinical studies have also highlighted the variable manifestations in children and identified potential factors associated with poorer outcomes. Consensus-based treatment guidelines are also appearing, but clinical trials are still essential to better understanding treatment efficacy and safety in children affected by AAV. New, validated outcome measures, including those that are patient-reported, will facilitate these much-needed clinical trials in pediatric AAV.
CONCLUSIONS: There is a continued need for more rigorous study in pediatric AAV, however, there is certainly excitement with the increase in recent research relevant to the pediatric population.

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.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV.
METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases.
RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients.
CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

OBJECTIVE: This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
METHODS: Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients.
RESULTS: The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown.
CONCLUSIONS: The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.