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Wilding S, Wu HHL, Brown N, Chinnadurai R. Anti-nuclear cytoplasmic antibody-associated vasculitis and kidney cancer: A mini review. World J Nephrol 2025; 14:105166. [DOI: 10.5527/wjn.v14.i2.105166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/26/2025] [Accepted: 03/08/2025] [Indexed: 04/09/2025] Open
Abstract
This mini review explores the links between anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and kidney cancer. Several studies suggest an increased incidence of cancer for patients with AAV. Different cancer types have shown different standardized incidence ratios (SIRs) in association with AAV. The SIRs of kidney cancer were found to be between 1.7 and 3.3 as per three retrospective data analyses. This association is likely multifactorial, with increased de novo cancer risks associated with inflammatory diseases; carcinogenic therapies such as cyclophosphamide; and reduced immune surveillance of neoplastic cells in immunocompromised individuals. Some studies have proposed that cancers, including kidney cancer, could be a potential trigger for AAV. Due to variability in SIRs and a lack of multicenter studies looking specifically into the incidence of kidney cancer at AAV diagnosis and on follow-up post initiation of AAV treatment, there remains a lack of evidence to support formal screening for kidney cancer in the AAV patient cohort. Greater awareness on the increased risk of cancer in AAV patients, prompt urological assessment of “red flag” symptoms of kidney cancer, and smoking cessation advice to reduce cancer risk should be standard of care for patients with AAV.
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Affiliation(s)
- Samuel Wilding
- Donal O’Donoghue Renal Research Center and Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
| | - Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital and The University of Sydney, Sydney 2065, Australia
| | - Nina Brown
- Donal O’Donoghue Renal Research Center and Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Donal O’Donoghue Renal Research Center and Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
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Bektaş M, Ince B, Zaralı S, Gülseren ÜA, Ük E, Ağargün BF, Güzey DY, Yalçınkaya Y, Artım-Esen B, Gul A, İnanç M. Damage accrual and predictors of mortality in ANCA-associated vasculitis: a retrospective observational study. Rheumatol Int 2025; 45:137. [PMID: 40332571 PMCID: PMC12058840 DOI: 10.1007/s00296-025-05883-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Accepted: 04/17/2025] [Indexed: 05/08/2025]
Abstract
In this study, we aimed to evaluate the factors affecting the development of damage and mortality in patients with AAV treated at our tertiary referral center. This retrospective study included data on patients with AAV who fulfilled the Chapel Hill Consensus Conference (CHCC) criteria. Patients were divided into c-ANCA/PR3( +) and p-ANCA/MPO ( +) groups based on ANCA immunofluorescence and/or ELISA results, and relapse, damage, and mortality data were compared across the groups. Data from 254 patients (n = 136, 53.5% female) were included in the analysis. Clinical diagnosis was GPA in 186 (73.2%) and MPA in 68 (26.8%) patients. During the follow-up, 217 of 242 (89.7%) patients developed damage, and the median VDI score of the cohort was 2 (IQR: 2). VDI scores were higher in the first period (1997-2011) than in the second period (2011-2021) in the entire cohort (p = 0.012) and in patients with GPA compared with MPA (p = 0.034). Five-year and overall survival rates were 88.1% and 80.3% in the entire cohort; 87.8% and 81% in c-ANCA/PR3 ( +); 86.2% and 76% in p-ANCA/MPO ( +) (Log-Rank: p = 0.35); 91% and 84.5% in GPA; 81% and 67.2% in MPA patients (Log-Rank: p < 0.001). Development of malignancy, severe infection, and active/persistent disease after the induction phase were associated with higher mortality in patients with AAV. In our AAV cohort, permanent organ damage was detected in the majority of the patients. Although the median VDI score decreased over time, mortality did not change.
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Affiliation(s)
- Murat Bektaş
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye.
- Department of Internal Medicine, Division of Rheumatology, Istanbul Aydın University, Istanbul, Türkiye.
| | - Burak Ince
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Sibel Zaralı
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Übeyde Ayşe Gülseren
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Ece Ük
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Besim Fazıl Ağargün
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Türkiye
| | | | - Yasemin Yalçınkaya
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Bahar Artım-Esen
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Ahmet Gul
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Murat İnanç
- Department of Internal Medicine, Division of Rheumatology Istanbul Faculty of Medicine, Istanbul, Türkiye
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3
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Yoon T, Yoon J, Ko E, Park YB, Lee SW. Clinical perspective on serum periostin in antineutrophil-cytoplasmic antibody-associated vasculitis. Korean J Intern Med 2025; 40:512-523. [PMID: 40360226 PMCID: PMC12081101 DOI: 10.3904/kjim.2024.254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/15/2024] [Accepted: 10/28/2024] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND/AIMS This study evaluated the clinical utility of serum periostin measured at diagnosis in reflecting activity at diagnosis and predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS This study included 76 patients with AAV whose serum periostin was measured from sera collected and stored at diagnosis. The correlation of either serum periostin or the Birmingham Vasculitis Activity Score (BVAS) with other variables was evaluated. Cumulative survival rates were compared using Kaplan-Meier survival analysis. The variables at diagnosis were compared between deceased and surviving patients. Hazard ratios were obtained by Cox proportional hazard analysis. RESULTS The median age of the 76 patients was 64.0 years and 60.5% were female. The median BVAS and serum periostin were 5.0 and 10.9 ng/mL, respectively. Five of the 76 patients (6.6%) died. Serum periostin was independently correlated with cross-sectional BVAS, the Vasculitis Damage Index (VDI), white blood cell count, and serum albumin. Patients with serum periostin ≥ 15.9 ng/mL at diagnosis had a significantly lower cumulative survival rate than those without. In addition to high VDI, dyslipidaemia frequency, and C-reactive protein, deceased patients showed higher serum periostin than surviving patients. In multivariable Cox analysis, however, only dyslipidaemia rather than serum periostin was identified as an independent predictor of all-cause mortality. CONCLUSION This study is the first to demonstrate that serum periostin at diagnosis could independently reflect cross-sectional BVAS and further partially contribute to all-cause mortality prediction in patients with AAV.
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Affiliation(s)
- Taejun Yoon
- Department of Medical Science, BK21 Plus Project, Yonsei University College of Medicine, Seoul,
Korea
| | - Jiyeol Yoon
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Eunhee Ko
- Department of Medical Science, BK21 Plus Project, Yonsei University College of Medicine, Seoul,
Korea
| | - Yong-Beom Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul,
Korea
| | - Sang-Won Lee
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul,
Korea
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Holle JU, Kubacki T, Aries P, Hellmich B, Kernder A, Kneitz C, Lamprecht P, Schirmer JH, Schreiber A, Berlit P, Bley TA, Blödt S, Decker L, de Groot K, Engel S, Jordans I, Frye B, Haubitz M, Holl-Ulrich K, Kötter I, Laudien M, Milger-Kneidinger K, Muche-Borowski C, Müller-Ladner U, Neß T, Nölle B, Reinhold-Keller E, Ruffer N, Scheuermann K, Venhoff N, von Vietinghoff S, Wiech T, Zänker M, Moosig F. [Diagnosis and treatment of ANCA-associated vasculitis : S3 guideline of the German Society for Rheumatology and Clinical Immunology e. V. (DGRh) and German Society for Internal Medicine e. V. (DGIM), German Society for Nephrology e. V. (DGfN), German Society for ENT Medicine and Head and Neck Surgery e. V. (DGHNO-KHC), German Ophthalmological Society e. V. (DOG), German Society for Neurology e. V. (DGN), German Society for Pneumology and Respiratory Medicine e. V. (DGP), German Society for Pathology e. V. (DGP), German Radiological Society, Society for Medical Radiology e. V. (DRG), Federal Association of German Pathologists, Federal Kidney Association e. V., German Rheumatism League Federal Association e. V.]. Z Rheumatol 2025; 84:1-49. [PMID: 40178542 DOI: 10.1007/s00393-024-01597-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2024] [Indexed: 04/05/2025]
Affiliation(s)
- J U Holle
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster/Kiel, Deutschland.
| | - T Kubacki
- Klinik für Innere Medizin II-Nephrologie, Rheumatologie, Diabetologie u. Allg. Innere Medizin, Universitätsklinikum Köln, Köln, Deutschland
| | - P Aries
- Immunologikum Hamburg, Hamburg, Deutschland
| | - B Hellmich
- Klinik für Innere Medizin, Rheumatologie, Pneumologie, Nephrologie, Medius Kliniken Nürtingen/Esslingen, Deutschland
| | - A Kernder
- Rheumazentrum Ruhrgebiet Herne, Ruhr-Universität Bochum, Bochum, Deutschland
| | - C Kneitz
- Rheumatologische Praxisgemeinschaft, Schwerin, Deutschland
| | - P Lamprecht
- Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Deutschland
| | - J H Schirmer
- Klinik für Innere Medizin I, Sektion Rheumatologie und klinische Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland
| | - A Schreiber
- Medizinische Klinik, Schwerpunkt Nephrologie, Charité Universitätsmedizin, Berlin, Deutschland
| | - P Berlit
- Deutsche Gesellschaft für Neurologie
| | - T A Bley
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | | | - L Decker
- Medizinisches Versorgungszentrum HNO Dormagen, Rheinland Klinikum, Dormagen, Deutschland
| | - K de Groot
- Klinik für Nephrologie und Rheumatologie, Sana Kliniken Offenbach, Offenbach, Deutschland
| | - S Engel
- Deutsche Rheuma-Liga Bundesverband e. V
| | | | - B Frye
- Department Innere Medizin, Klinik für Pneumologie, Universitätsklinikum Freiburg, Freiburg, Deutschland
| | - M Haubitz
- Medizinische Klinik III (Nephrologie), Klinikum Fulda, Fulda, Deutschland
| | - K Holl-Ulrich
- Konsultations- und Referenzzentrum für Vaskulitisdiagnostik, Labor Lademannbogen, Hamburg, Deutschland
| | - I Kötter
- III. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland
| | - M Laudien
- Klinik für HNO-Heilkunde, Kopf- und Halschirurgie, Christian-Albrechts-Universität zu Kiel, Kiel, Deutschland
- Deutsche Gesellschaft für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie e. V., Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland
| | - K Milger-Kneidinger
- Medizinische Klinik und Poliklinik V, Ludwig-Maximilians-Universität München, München, Deutschland
| | | | - U Müller-Ladner
- Abteilung für Rheumatologie und Klinische Immunologie, Justus-Liebig-Universität, Gießen, Campus Kerckhoff, Bad Nauheim, Deutschland
| | - T Neß
- Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Deutschland
| | - B Nölle
- Klinik für Ophthalmologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland
| | | | - N Ruffer
- III. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Arbeitsgemeinschaft Junge Rheumatologie, Deutsche Gesellschaft für Rheumatologie e. V., Berlin, Deutschland
| | | | - N Venhoff
- Klinik für Rheumatologie und Klinische Immunologie, Vaskulitis-Zentrum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg, Deutschland
| | - S von Vietinghoff
- Medizinische Klinik und Poliklinik I, Sektion für Nephrologie, Universitätsklinikum Bonn und Universität Bonn, Bonn, Deutschland
| | - T Wiech
- Institut für Pathologie, Sektion Nephropathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - M Zänker
- Klinik für Innere Medizin, Rheumatologie, Nephrologie, Immanuel Klinikum Bernau, Medizinische Hochschule Brandenburg, Deutschland
| | - F Moosig
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster/Kiel, Deutschland
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Schaier M, Kälble F, Benning L, Reichel P, Mahler C, Nusshag C, Rusnak J, Gutting T, Preusch M, Zeier M, Morath C, Speer C. ANCA-associated vasculitis and the impact of diffuse alveolar hemorrhage in elderly patients: a retrospective cohort study. Rheumatol Int 2025; 45:68. [PMID: 40029448 PMCID: PMC11876205 DOI: 10.1007/s00296-025-05812-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 02/10/2025] [Indexed: 03/05/2025]
Abstract
The ANCA-associated vasculitis (AAV) has an exceptionally high morbidity and mortality especially in patients with diffuse alveolar hemorrhage (DAH). Data on DAH in elderly AAV patients is still very limited. To investigate the impact of DAH on patient survival, relapse-free survival, death from infectious complications, and the incidence of pneumonia in one of the most vulnerable but often underrepresented AAV subpopulation-elderly patients. We included 139 AAV patients in this retrospective cohort study and performed a 5-year follow-up. AAV patients were divided into patients ≤ 65 and > 65 years ("elderly"). Elderly AAV patients were further subdivided into patients with and without DAH. Relapse-free survival was comparable (P = 0.49) whereas overall patient survival (P = 0.01) was significantly lower in patients > 65 as compared to ≤ 65 years. Death due to infectious complications occurred more frequently in the elderly cohort (log-rank P = 0.02). Especially the incidence of pneumonia (including opportunistic pathogens) was considerably higher in elderly AAV patients (log-rank P = 0.001). Overall survival in elderly patients was significantly lower in patients with as compared to patients without DAH [8/18 (44%) versus 9/52 (17%) deaths (P = 0.02)] while relapse-free survival was again comparable (P = 0.87) between both groups. Notably, 6 out of 8 fatal outcomes in elderly DAH patients were associated with severe infections. In multivariate analyses, age and glucocorticoid (GC) dose at 3 months were the only predictors of death from infectious complications, whereas this could not be independently demonstrated for DAH. Life-threatening infections with (opportunistic) pneumonia are common in elderly AAV patients with DAH during the first 12 months and higher GC dose was an independent predictor of death from infectious complications.
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Affiliation(s)
- Matthias Schaier
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Florian Kälble
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Louise Benning
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Paula Reichel
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Christoph Mahler
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Christian Nusshag
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Jonas Rusnak
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University, Heidelberg, Germany
| | - Tobias Gutting
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University, Heidelberg, Germany
| | - Michael Preusch
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University, Heidelberg, Germany
| | - Martin Zeier
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Christian Morath
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany
| | - Claudius Speer
- Department of Nephrology, Heidelberg University, INF 162, 69120, Heidelberg, Germany.
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University, Heidelberg, Germany.
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McGovern DP, Jones RB, Jayne DRW, Smith RM. The Expanding Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Armamentarium. Drugs 2025; 85:325-341. [PMID: 39969779 DOI: 10.1007/s40265-024-02143-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2024] [Indexed: 02/20/2025]
Abstract
The complex pathophysiology of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is reflected in the heterogeneity of the presenting clinical syndromes caused by these diseases but also provides a variety of conceivable molecular and cellular targets that can be therapeutically manipulated. The last decade has seen an expansion of established and potential therapies for treating AAV, some of which target the dysfunctional autoreactive immune response and others aim to ameliorate the downstream consequences of local vascular inflammation and necrosis. The success and widespread adoption of the anti-CD20 monoclonal antibody, rituximab, as an agent to both induce and maintain remission, has heralded a change in the standard-of-care management of AAV, replacing the "old guard" combination of cyclophosphamide and high-dose corticosteroids established in the 1970s. The development and approval of avacopan, a first-in-class small-molecule antagonist to the main receptor for the complement anaphylatoxin C5a, has the potential to reduce the corticosteroid burden experienced by patients with AAV and may also improve outcomes for those with AAV kidney disease. It marks the culmination of almost 20 years of international collaboration, from understanding the pathological role of complement in basic murine models of AAV through to a phase III clinical trial, and emphasises the importance of following promising translational discoveries through to drug development and clinical deployment. This article summarises how recent progress in our understanding of the basic pathophysiology of AAV has resulted in the development of new and effective treatments and, reciprocally, how studying the impact of these treatments in patients has advanced our understanding of dysfunctional immunobiology in disease.
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Affiliation(s)
- Dominic P McGovern
- Vasculitis Research Group, Department of Medicine, Addenbrooke's Hospital Level 5, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK.
- Cambridge Lupus and Vasculitis Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
| | - Rachel B Jones
- Vasculitis Research Group, Department of Medicine, Addenbrooke's Hospital Level 5, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
- Cambridge Lupus and Vasculitis Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - David R W Jayne
- Vasculitis Research Group, Department of Medicine, Addenbrooke's Hospital Level 5, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
- Cambridge Lupus and Vasculitis Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rona M Smith
- Vasculitis Research Group, Department of Medicine, Addenbrooke's Hospital Level 5, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
- Cambridge Lupus and Vasculitis Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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7
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Katz G, Cook CE, Fu X, King AJ, Stone JH, Choi HK, Wallace ZS. Defining cause of death in a contemporary cohort with ANCA-associated vasculitis (AAV): A comparison of electronic health record and death certificate data. Semin Arthritis Rheum 2025; 70:152609. [PMID: 39733485 PMCID: PMC11772007 DOI: 10.1016/j.semarthrit.2024.152609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/06/2024] [Accepted: 12/12/2024] [Indexed: 12/31/2024]
Abstract
OBJECTIVES Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) face excess mortality compared with the general population. Mortality in clinical epidemiology research is often examined using death certificate diagnosis codes; however, the sensitivity of such codes in AAV is unknown. METHODS We performed a retrospective cohort study using the Mass General Brigham AAV Cohort, including patients with AAV who died between 2002 and 2019. Causes of death were determined by electronic health record (EHR) review (reference gold standard) and via cause of death diagnosis codes on death certificates. We calculated the sensitivity of death certificate diagnosis codes for AAV. RESULTS Of 684 patients in the registry, 184 died, 92 (52 %) of whom had adequate EHR data available determine cause of death and 72 (40 %) of whom had both EHR and death certificate data available. Death due to AAV, infection, cardiovascular disease, and cancer occurred in 8 %, 29 %, 5 %, and 18 %, respectively, when ascertained by manual review, as opposed to 0 %, 11 %, 25 %, and 21 %, as determined by death certificates. The sensitivity of AAV diagnosis codes for AAV was 16.6 % (95 % CI: 10.5, 22.6) among all patients with death certificate data available. CONCLUSION In a contemporary cohort of patients with AAV, infection was the most common cause of death, while death due to AAV itself was rare. We found a high degree of discordance between causes of death determined by manual review and death certificate diagnosis codes. Mortality research on AAV should include linkage to medical records data to reduce potential bias.
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Affiliation(s)
- Guy Katz
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA.
| | - Claire E Cook
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - Xiaoqing Fu
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - Andrew J King
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - John H Stone
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - Hyon K Choi
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
| | - Zachary S Wallace
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Yawkey 4B, Boston, MA, USA
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8
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Luo W, Liu C, Zhang L, Tang J, Chen J, Zhao Y, Huang X, Zheng X, Chen L, Xie C, Wei X, Luo X, Xiong A. Characteristics and risk factors for infection in patients with ANCA-associated vasculitis: A systematic review and meta-analysis. Autoimmun Rev 2025; 24:103713. [PMID: 39617249 DOI: 10.1016/j.autrev.2024.103713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/27/2024] [Accepted: 11/27/2024] [Indexed: 12/07/2024]
Abstract
OBJECTIVE To summarize the characteristics and risk factors for infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS PubMed, Embase, and Cochrane Library databases were searched for relevant articles from database inception to November 2023. The prevalence, odds ratio (OR), and mean difference (MD) with 95 % confidence intervals (CIs) were pooled using a random-effects model. Sensitivity and subgroup analysis were also performed. RESULTS Forty-one studies with 5343 patients with AAV were included, of whom 2890 patients experienced an infection. The pooled prevalence was 54.6 % (95 % CI, 48.4 % to 61.1 %) for all infections and 35.8 % (95 % CI, 31.0 % to 40.8 %) for severe infections; and prevalence of Pneumocystis jirovecii pneumonia, aspergillosis, candidiasis, cryptococcosis, herpes zoster, cytomegalovirus, and specific bacterial infections were pooled. The respiratory system was the most common infection site, followed by blood, urinary tract, skin and soft tissue, and digestive infections. Risk factors for infection included older age, end-stage renal disease, dialysis, diabetes, smoking, kidney and lung involvement, leukopenia; higher Birmingham Vasculitis Activity Score, and serum creatinine and C-reactive protein levels; and lower hemoglobin levels, and platelet and CD4 counts. In addition, use of cyclophosphamide, steroid pulse therapy, plasma exchange, and higher initial glucocorticoid dose were associated with significantly increased risk of infection. CONCLUSION In patients with AAV, therapy should take risk factors for infection into account. Risk factors should be modified wherever possible. Physicians should be familiar with the common infection sites and pathogens, and consider empiric therapy covering common pathogens for life-threatening infections.
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Affiliation(s)
- Wenxuan Luo
- Department of Rheumatology and Immunology, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Can Liu
- Department of Rheumatology and Immunology, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Lei Zhang
- Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jie Tang
- Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jie Chen
- Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yanzao Zhao
- Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xuemei Huang
- Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xiaoli Zheng
- School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Long Chen
- Department of Rheumatology and Immunology, Suining Central Hospital, Suining, Sichuan, China
| | - Chuanmei Xie
- Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xin Wei
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Xiongyan Luo
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Anji Xiong
- Department of Rheumatology and Immunology, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China; Inflammation and Immunology Key Laboratory of Nanchong City, Nanchong, Sichuan, China; Nanchong Central Hospital, (Nanchong Clinical Research Center), Nanchong, Sichuan, China.
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9
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Do H, Yoon T, Park YB, Ha JW, Ahn SS, Lee SW. Prediction potential of serum sulfatide levels at diagnosis for end-stage kidney disease progression in ANCA-associated vasculitis. Medicine (Baltimore) 2025; 104:e41271. [PMID: 39889196 PMCID: PMC11789854 DOI: 10.1097/md.0000000000041271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 12/12/2024] [Accepted: 01/02/2025] [Indexed: 02/02/2025] Open
Abstract
The aim was to investigate the ability of serum sulfatide levels at diagnosis to reflect the cross-sectional activity and further longitudinally predict the occurrence of end-stage kidney disease (ESKD) during the follow-up period in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), regardless of kidney involvement at diagnosis. This study included 67 patients first diagnosed with AAV with available clinical data, including Birmingham Vasculitis Activity Score (BVAS), erythrocyte sedimentation rate, C-reactive protein, and blood samples at diagnosis. Serum sulfatide levels were assessed using stored serum samples at the time of diagnosis. The median age of the 67 patients (40.3% men and 59.7% women) was 61.0 years. During follow-up, 10 (14.9%) patients progressed to ESKD, and 4 (6.0%) died. Serum sulfatide levels significantly correlated with Five-Factor Score (r = -0.242), erythrocyte sedimentation rate (r = -0.315), and renal manifestation of the BVAS items (r = -0.296), but not BVAS at diagnosis. The cutoff of serum sulfatide levels at diagnosis for ESKD progression was 332.5 pg/mL. However, no significant cutoff of serum sulfatide levels for all-cause mortality was obtained. Patients with serum sulfatide levels ≤ 332.5 pg/mL at diagnosis exhibited both significantly higher frequency of ESKD progression (22.7% vs 0%, P = .012) and lower ESKD-free survival rate than those without (P = .011). This study highlighted the clinical usefulness of measuring serum sulfatide levels at the time of diagnosis as a biomarker to predict ESKD progression in patients with AAV regardless of kidney involvement at diagnosis.
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Affiliation(s)
- Hyunsue Do
- Department of Internal Medicine, Division of Rheumatology, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea
| | - Taejun Yoon
- Department of Medical Science, BK21 Plus Project, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Yong-Beom Park
- Department of Internal Medicine, Division of Rheumatology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jang Woo Ha
- Department of Internal Medicine, Division of Rheumatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Republic of Korea
| | - Sung Soo Ahn
- Department of Internal Medicine, Division of Rheumatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Republic of Korea
| | - Sang-Won Lee
- Department of Internal Medicine, Division of Rheumatology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
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10
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Park PG, Yoon J, Park YB, Lee SW. A New Formula Consisting of the Initial Independent Predictors of All-Cause Mortality Derived from a Single-Centre Cohort of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. J Clin Med 2025; 14:779. [PMID: 39941450 PMCID: PMC11818776 DOI: 10.3390/jcm14030779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/08/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
Objective: In this study, we develop a new formula for predicting all-cause mortality in an ethnicity/region-specific cohort of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: We included 290 Korean patients with AAV in this study and retrospectively reviewed their medical records regarding clinical data at diagnosis and during follow-up. We introduce a new index, called the NFPM value after the initials of New Formula for Predicting Mortality, which we derived using the independent predictors of all-cause mortality obtained in the multivariable Cox proportional hazard analysis. The cut-offs of the parameters for mortality were determined using the highest or lowest tertile of each parameter according to its positive or negative association with all-cause mortality, respectively. Results: The median age was 60.0 years and 35.9% were male patients. Of the 290 patients, 39 died during follow-up (13.4%). In the multivariable Cox analysis, male sex, the five-factor score (FFS), and serum albumin were independent predictors of all-cause mortality. A new formula was developed as follows: NFPM = male sex (yes = 1 or no = 0) + FFS ≥ 2.0 (yes = 1 or no = 0) + serum albumin ≤ 3.2 mg/dL (yes = 1 or no = 0). We demonstrated that patients with a NFPM value ≥ 2 seemed to have an increased risk for all-cause mortality compared to those with a NFPM value < 2. Conclusions: This study demonstrated that it could be clinically useful and significant to develop a new formula to predict all-cause mortality using independent predictors in each different ethnicity/region-specific cohort of AAV.
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Affiliation(s)
- Pil Gyu Park
- Division of Rheumatology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang 10444, Republic of Korea;
| | - Jiyeol Yoon
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Yong-Beom Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Sang-Won Lee
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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11
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Hendrickson M, Parakh A, Weber B, Cook C, Ahola C, Hedgire S, Lu M, Wallace ZS. Burden of coronary artery calcification in ANCA-associated vasculitis. RMD Open 2025; 11:e004774. [PMID: 39762122 PMCID: PMC11748941 DOI: 10.1136/rmdopen-2024-004774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/26/2024] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is a leading cause of death in ANCA-associated vasculitis (AAV). Screening and primary cardiovascular prevention may improve outcomes. METHODS We identified patients in the 2002-2019 Mass General Brigham AAV cohort with thoracic CT scans obtained for other clinical purposes. Coronary artery calcium (CAC) scores and age, sex and race-standardised CAC percentiles were calculated. Quantile regression was used to identify differences by ANCA type, and Gray's test examined differences in major adverse cardiac events by CAC score. RESULTS Of 175 included patients, 127 (73%) were MPO-ANCA+and 48 (27%) were PR3-ANCA+. The median CAC score was 17 (IQR 0, 334) and CAC percentile was 45 (IQR 0, 78); 65 (39%) patients had CAC of ≥100. The total CAC score was higher in patients with MPO-ANCA+AAV vs PR3-ANCA+AAV (median 24 vs 1, p=0.003), as was the standardised CAC percentile (50th vs 34th, p=0.02). Of 116 (66%) patients with non-zero CAC scores, only 29 (25%) were on a statin. In a time-to-event analysis, CAC of 100 or higher trended towards association with higher risk of major adverse cardiovascular events (χ2=1.9, p=0.16). CONCLUSION A majority of patients with AAV had clinically significant CAC. There were differences in CAC burden among those with MPO-ANCA+AAV versus PR3-ANCA+AAV. Although CAC is associated with CVD risk and an indication for statins, the use was inconsistent. The role of CT imaging to screen for CVD and guide primary prevention in AAV requires further study.
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Affiliation(s)
- Michael Hendrickson
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Anushri Parakh
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Brittany Weber
- Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Claire Cook
- Rheumatology and Allergy Clinical Epidemiology Research Center, MGH, Boston, Massachusetts, USA
| | - Catherine Ahola
- Rheumatology and Allergy Clinical Epidemiology Research Center, MGH, Boston, Massachusetts, USA
| | - Sandeep Hedgire
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Michael Lu
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Zachary S Wallace
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Rheumatology and Allergy Clinical Epidemiology Research Center, MGH, Boston, Massachusetts, USA
- Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, MA, USA
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12
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Long LL, Tan M, Deng H, Tang H, Lin XQ, Zhang M, Deng HY, Gao X. Comparison of the clinicopathological characteristics of children with anti-neutrophil cytoplasmic antibody-associated vasculitis with/without infection at diagnosis. BMC Nephrol 2025; 26:7. [PMID: 39762790 PMCID: PMC11706063 DOI: 10.1186/s12882-024-03919-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Infectious episodes contribute to morbidity and mortality in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is frequently observed in AAV. Little is known about whether co-infection at initial diagnosis is associated with renal outcome and prognosis in children with AGN. METHODS Clinical and prognostic data for children admitted to our center with AAV from January 2001 to August 2023 were analyzed retrospectively. We compared the incidence of end-stage renal disease (ESRD) and mortality according to infection status at initial diagnosis. RESULTS A total of 33 children with AGN were included in this study, 22 had an infection at the time of AGN diagnosis. A trend toward higher levels of proteinuria in the infected group than in the non-infected group was observed (p = 0.42). Patients in the infected group had higher creatinine and lower eGFR values than those in the non-infected group (p = 0.09). A significant decrease in HGB was observed in the infected group (p < 0.05). There were no significant differences in the baseline values of ALB and complement c3 between the two groups. A similar proportion of patients in both groups required dialysis at the time of diagnosis (27.3% vs. 31.8%). Patients with infection presented with significantly greater ESR and CRP levels (p < 0.05), and the most commonly infected site was the lung. After 6 months of treatment, compared with those in the non-infected group, the median levels of creatinine and proteinuria were higher in the infected group. Besides, lower levels of eGFR and ALB were also observed in the infected group. 5 (45.5%) and 13 (59.1%) patients died or progressed to ESRD, respectively, in the non-infected group and infected group at the last follow-up. CONCLUSIONS Infection at initial diagnosis does not affect the outcomes of children with AGN, although it could lead to a reduction in kidney function.
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Affiliation(s)
- Li-Li Long
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Mei Tan
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Hui Deng
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Hui Tang
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Xiao-Qing Lin
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Miao Zhang
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Hui-Ying Deng
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Xia Gao
- Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
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13
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Hendrickson MJ, Wallace ZS. Mechanisms and Screening for Atherosclerosis in Adults With Vasculitis. Arterioscler Thromb Vasc Biol 2025; 45:3-10. [PMID: 39569518 DOI: 10.1161/atvbaha.124.319982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
Vascular inflammation is a hallmark of both primary systemic vasculitis and atherosclerosis. As such, cardiovascular events are common in patients with vasculitis and likely due to both direct vascular inflammation and accelerated atherosclerosis. Direct cardiac involvement is possible in all vasculitides, though more commonly described in Takayasu arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis. Accelerated atherosclerosis has been described in Takayasu arteritis and antineutrophil cytoplasmic antibody-associated vasculitis, though there remains a paucity of data in other forms of vasculitis. Multiple screening and management approaches for cardiovascular risk in people with vasculitis have been proposed, though evidence-based guidelines are lacking. In this review, we discuss the latest evidence in epidemiology, mechanisms, and screening for atherosclerosis in patients with primary systemic vasculitides.
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Affiliation(s)
- Michael J Hendrickson
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (M.J.H., Z.S.W.)
| | - Zachary S Wallace
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (M.J.H., Z.S.W.)
- Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston (Z.S.W.)
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14
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Ivković V, Windpessl M, Berke I, Geetha D, Callemeyn J, Norouzi S, Bajema IM, Kronbichler A. ANCA-Associated Glomerulonephritis: Diagnosis and Therapy Proceedings of the Henry Shavelle Lectureship. GLOMERULAR DISEASES 2025; 5:26-47. [PMID: 39991195 PMCID: PMC11842095 DOI: 10.1159/000542925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 11/29/2024] [Indexed: 02/25/2025]
Abstract
Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently affects the kidney. Glomerulonephritis (GN) in AAV, ANCA-GN, not only dictates therapeutic decisions but is also of relevance for overall survival influencing the risk of cardiovascular disease and serious infections. Summary A diagnosis of ANCA-GN includes laboratory investigations including urinalysis and a thorough assessment of potential organ involvement. A kidney biopsy can be performed to ascertain the diagnosis but has an additional prognostic relevance and tools have been established to predict long-term kidney survival. Experimental biomarkers indicating kidney inflammation include urinary soluble CD163 and the presence of urinary T cells. Therapeutic options are refined and some of these therapies, such as the added value of performing plasma exchange, are the matter of controversial discussions. Safe reduction of cumulative exposure to glucocorticoids and eventually the use of avacopan to substantially reduce glucocorticoid exposure has been implemented in most centers. In the remission of maintenance, the optimal duration of therapy is still unclear, but extended use of rituximab as maintenance agent has shown long-term remission rates, thus limiting the damage accrued by relapsing disease and thus also reducing the risk of end-stage kidney disease (ESKD). Avacopan has been the first agent with a glomerular filtration rate-sparing effect, likely due to more rapid control of kidney inflammation. Those reaching ESKD should be evaluated for kidney transplantation and the risk of remaining on dialysis must be balanced against the risk of recurrence of disease following transplantation. Key Messages The advent of a magnitude of landmark studies in ANCA-GN has refined diagnostic approaches, implemented tools to predict kidney outcome, and eventually led to the approval of newer therapies with avacopan, the latest addition to the armamentarium. Once ESKD is present, patients should be considered for kidney transplantation as remaining on dialysis portends poor overall prognosis.
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Affiliation(s)
- Vanja Ivković
- Department of Internal Medicine, Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
- University of Rijeka Faculty of Health Studies, Rijeka, Croatia
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Martin Windpessl
- Department of Internal Medicine IV, Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Ilay Berke
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
| | - Duvuru Geetha
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jasper Callemeyn
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Leuven, Belgium
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Sayna Norouzi
- Division of Nephrology, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Ingeborg M. Bajema
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands
| | - Andreas Kronbichler
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
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15
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Morales E, Rúa-Figueroa I, Callejas Rubio JL, Ávila Bernabéu A, Blanco Alonso R, Cid Xutgla MC, Fernández Juárez G, Mena-Vázquez N, Ríos Blanco JJ, Manrique Escola J, Narváez García FJ, Sopeña B, Quintana Porras LF, Romero-Yuste S, Solans Laqué R. Recommendations for the diagnosis and treatment of anti-neutrophil cytoplasmic autoantibody associated vasculitis. Nefrologia 2025; 45:15-58. [PMID: 39855968 DOI: 10.1016/j.nefroe.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 07/30/2024] [Indexed: 01/27/2025] Open
Abstract
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is characterised by small vessel necrotising inflammatory vasculitis. Prior to immunosupressant therapy availability it usually led to a fatal outcome. Current treatment has changed ANCA-associated vasculitis into a condition with a significant response rate, although with a not negligible relapse occurrence and cumulative organ lesions, mostly due to drug-related toxicities. The use of glucocorticoids, cyclophosphamide and other immunosupressants (such as azathioprine, mychophenolate and methotrexate) was optimised in a series of clinical trials that established the treatment of reference. In recent years, a better knowledge of B lymphocyte function and the role of complement inhibition has transformed the course of this disease while minimising treatment-related adverse effects. This multidisciplinary document of recommendations is based on the consensus of three scientific societies (Internal Medicine, Nephrology and Rheumatology) and on the best available evidence on diagnosis, treatment and follow-up of patients with ANCA-associated vasculitis, including some special situations. The aim of this document is to provide updated information and well-grounded clinical recommendations to practising physicians as to how to improve the diagnosis and treatment outcome of our patients.
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Affiliation(s)
- Enrique Morales
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de investigación i + 12 de Hospital 12 de Octubre, Departamento de Medicina de la Universidad Complutense de Madrid, Madrid, Spain.
| | - Iñigo Rúa-Figueroa
- Servicio de Reumatología, Hospital de Gran Canaria Doctor Negrín, Las Palmas, Spain
| | - José Luis Callejas Rubio
- Unidad de Enfermedades Sistémicas, Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Ana Ávila Bernabéu
- Servicio de Nefrología, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Ricardo Blanco Alonso
- Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - María C Cid Xutgla
- Servicio de Enfermedades Autoinmunes, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | | | - Natalia Mena-Vázquez
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Juan José Ríos Blanco
- Unidad de Enfermedades Autoinmunes, Servicio de Medicina Interna, Hospital Universitario La Paz, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
| | | | | | - Bernardo Sopeña
- Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Clínico Universitario de Santiago, Facultad de Medicina, Santiago de Compostela, Spain
| | - Luis F Quintana Porras
- CSUR Enfermedad Glomerular Compleja, Servicio de Nefrología y Trasplante Renal, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain
| | - Susana Romero-Yuste
- Servicio de Reumatología, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - Roser Solans Laqué
- Unidad de Enfermedades Sistémicas Autoinmunes, Departamento de Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, Spain
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16
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Goyal A, Abbasi HQ, Mashkoor Y, Khan AM, Sulaiman SA, Daoud M, Bansal K. Assessment of cardiovascular risk in patients with ANCA-associated vasculitis: A systematic review and meta-analysis. INTERNATIONAL JOURNAL OF CARDIOLOGY. CARDIOVASCULAR RISK AND PREVENTION 2024; 23:200334. [PMID: 39417001 PMCID: PMC11481614 DOI: 10.1016/j.ijcrp.2024.200334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/26/2024] [Accepted: 09/19/2024] [Indexed: 10/19/2024]
Abstract
Background Although many chronic inflammatory conditions are linked to elevated cardiovascular risk, the specific extent of this risk in ANCA-associated vasculitis (AAV) remains elusive, largely due to the disease's rarity. Our study sought to clarify the cardiovascular risks and mortality linked to AAV. Methods A systematic literature review was conducted across multiple databases from their inception until April 2024 to identify studies comparing cardiovascular outcomes in patients with and without AAV. R Studio's meta package was used to pool risk ratios under the random-effects model, and statistical significance was set at p < 0.05. Results Nine observational studies involving 45024 individuals were included in this analysis. Patients with AAV exhibited a significantly elevated risk of stroke (RR = 1.43, 95 % CI: 1.12-1.83, I2 = 62 %, p = 0.0048), myocardial infarction (RR = 1.49, 95 % CI: 1.25-1.79, I 2 = 0 %, p < 0.0001), ischemic heart disease (RR = 1.40, 95 % CI: 1.24-1.58, I 2 = 1 %, p < 0.0001), venous thromboembolism (RR = 2.57, 95 % CI: 1.70-3.90, I 2 = 74 %, p < 0.0001), and pulmonary embolism (RR = 3.53, 95 % CI: 2.82-4.42, I 2 = 9 %, p < 0.0001), deep vein thrombosis (RR: 4.21; 95 % CI: 2.00-8.86; p = 0.0002), heart failure (RR = 1.63, 95 % CI: 1.39-1.90, I 2 = 0 %, p < 0.0001), and cardiovascular disease-related mortality (RR = 1.79, 95 % CI: 1.07-3.00, I2 = 0 %, p = 0.0256) compared to patients without AAV. Conclusion This meta-analysis underscores a notable increase in adverse cardiovascular events among patients with AAV, underscoring the need for comprehensive cardiovascular care and diligent monitoring in this patient cohort.
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Affiliation(s)
- Aman Goyal
- Department of Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, India
| | | | - Yusra Mashkoor
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Abdul Moiz Khan
- Department of Internal Medicine, Ayub Medical College, Abbottabad, Pakistan
| | | | - Mohamed Daoud
- Department of Internal Medicine, Bogomolets National Medical University, Kyiv, Ukraine
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17
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Angioi A, Cheungpasitporn W, Lepori N. Management of immune-mediated glomerular diseases in the elderly. Ren Fail 2024; 46:2411848. [PMID: 39378123 PMCID: PMC11463022 DOI: 10.1080/0886022x.2024.2411848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 09/25/2024] [Accepted: 09/27/2024] [Indexed: 10/10/2024] Open
Abstract
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.
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Affiliation(s)
- Andrea Angioi
- S.C.D.U. Nefrologia, Dialisi e Trapianto, ARNAS Brotzu, Cagliari, Italy
| | | | - Nicola Lepori
- S.C.D.U. Nefrologia, Dialisi e Trapianto, ARNAS Brotzu, Cagliari, Italy
- Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy
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18
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Ho CM, Mok CC. Rituximab for Induction Therapy of ANCA-Associated Vasculitis: Practical Issues in the Asia Pacific Region. Int J Rheum Dis 2024; 27:e70016. [PMID: 39673216 DOI: 10.1111/1756-185x.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/09/2024] [Indexed: 12/16/2024]
Affiliation(s)
- Cheuk Man Ho
- Department of Medicine & Geriatrics, Pok Oi Hospital, Au Tau, Hong Kong
| | - Chi Chiu Mok
- Department of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong
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Misra DP, Rathore U, Jagtap S, Mishra P, Thakare DR, Singh K, Qamar T, Singh D, Dixit J, Behera MR, Jain N, Ora M, Bhadauria DS, Gambhir S, Agarwal V, Kumar S. Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study. J Rheumatol 2024; 51:1187-1192. [PMID: 38561192 DOI: 10.3899/jrheum.2023-1254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVE To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.
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Affiliation(s)
- Durga Prasanna Misra
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences;
| | - Upendra Rathore
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Swapnil Jagtap
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Prabhaker Mishra
- P. Mishra, PhD, Department of Biostatistics and Health Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Darpan R Thakare
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Kritika Singh
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Tooba Qamar
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Deeksha Singh
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Juhi Dixit
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Manas Ranjan Behera
- M.R. Behera, MD, DM, Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Neeraj Jain
- N. Jain, DNB, Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Manish Ora
- M. Ora, MD, S. Gambhir, DNB, Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Dharmendra Singh Bhadauria
- D.S. Bhadauria, MD, DM, Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Sanjay Gambhir
- M. Ora, MD, S. Gambhir, DNB, Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Vikas Agarwal
- D.P. Misra, MD, DM, MSc, U. Rathore, MD, DM, S. Jagtap, MD, D.R. Thakare, MD, K. Singh, MSc, T. Qamar, MSc, D. Singh, MTech, J. Dixit, MD, DNB, DM, V. Agarwal, MD, DM, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences
| | - Sudeep Kumar
- S. Kumar, MD, DM, Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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20
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Manole OM, Haba MȘC, Matei IT, Onofrei V. Rare Clinical Manifestation of Vasculitis. Diagnostics (Basel) 2024; 14:2623. [PMID: 39682532 DOI: 10.3390/diagnostics14232623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/15/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation. METHODS We present an atypical cardiac scenario of p-ANCA vasculitis. RESULTS A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina. CONCLUSIONS This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls.
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Affiliation(s)
- Oana-Mădălina Manole
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiology, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Mihai Ștefan Cristian Haba
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiology, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Iulian-Theodor Matei
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiology, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Viviana Onofrei
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiology, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iași, Romania
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21
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Chen R, Shi Y, Sun H, Xu K, Li Z, Wang M, Shao C, Huang H. Prognostic analysis of Pneumocystis jirovecii pneumonia in patients with systemic vasculitides: a retrospective cohort study. Clin Rheumatol 2024; 43:3419-3429. [PMID: 39305386 PMCID: PMC11489196 DOI: 10.1007/s10067-024-07149-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 09/04/2024] [Accepted: 09/16/2024] [Indexed: 10/03/2024]
Abstract
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.
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Affiliation(s)
- Ruxuan Chen
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yujie Shi
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Hongli Sun
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Kai Xu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Peking Beijing, 100730, China
| | - Zhiyi Li
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Mengqi Wang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Chi Shao
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Hui Huang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
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22
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Sattui SE, Jiang B, Fu X, Cook C, Srivatsan S, Williams ZK, Katz G, Zhang Y, Wallace ZS. The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study. THE LANCET. RHEUMATOLOGY 2024; 6:e771-e779. [PMID: 39305914 DOI: 10.1016/s2665-9913(24)00193-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/18/2024] [Accepted: 06/28/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. FINDINGS Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). INTERPRETATION Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. FUNDING National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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Affiliation(s)
- Sebastian E Sattui
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Bohang Jiang
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Xiaoqing Fu
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Claire Cook
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Shruthi Srivatsan
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Zachary K Williams
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Guy Katz
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Yuqing Zhang
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Zachary S Wallace
- Rheumatology and Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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23
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Giardini HAM, Caparbo VDF, de Castro I, Toledo AP, Barbas CSV, Shinjo SK, Pereira RMR. Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients. Clinics (Sao Paulo) 2024; 79:100524. [PMID: 39476516 PMCID: PMC11565043 DOI: 10.1016/j.clinsp.2024.100524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/12/2024] [Accepted: 10/13/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Alpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients. OBJECTIVE The present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups. METHODS In this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes. RESULTS The authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years). CONCLUSION SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.
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Affiliation(s)
- Henrique Ayres Mayrink Giardini
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
| | - Valeria de Falco Caparbo
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Isac de Castro
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Andréia Padilha Toledo
- Pneumology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Carmen Silvia Valente Barbas
- Pneumology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Samuel Katsuyuki Shinjo
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Rosa Maria Rodrigues Pereira
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
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Li H, Yu J, Zeng Z, Liu C, Zhang Y, Xia H, Guo S. Clinical and pathological features of cerebrospinal meningitis caused by Pantoea agglomerans : a case report. BMC Infect Dis 2024; 24:1150. [PMID: 39396943 PMCID: PMC11472509 DOI: 10.1186/s12879-024-10035-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 10/01/2024] [Indexed: 10/15/2024] Open
Abstract
BACKGROUND Pantoea agglomerans (P. agglomerans) is a gram-negative bacterium that is commonly isolated from plant surfaces, seeds, and the environment. As an opportunistic pathogen, it can cause blood, urinary and soft tissue infections in immunocompromised patients. In central nervous system, P. agglomerans infection has been report in children and immune-compromised patients, however, infection by such bacterium in nontraumatized immune competent adults has not been reported. Here, we report a case of P. agglomerans cerebrospinal meningitis accompanied by positive anti-myeloperoxidase (MPO) antibody in a 49-year-old female who has a history of black fungus planting. CASE PRESENTATION The patient manifested with repeated fever, headache, generalized muscle pain, and neurological defects. Cerebrospinal fluid (CSF) tests revealed a moderately elevated number of polymorphonuclear leukocytes (50-193 × 106/L), low glucose levels (0.54-2.44 mmo1/L), and extremely high protein content (2.42-25.42 g/L). Blood tests showed positive anti-myeloperoxidase antibodies lasting for 1.5 year before turning negative. Spine MRI showed thickening and enhancement of the whole spinal meninges. CSF metagenomic next-generation sequencing (mNGS) revealed 75,189 specific DNA reads of P. agglomerans. The patient underwent spinal laminectomy due to meningeal adhesions. Pathological results revealed fibrous tissue proliferation, inflammatory infiltration with focal necrosis and calcification in the dura mater. The patient was successfully treated with sufficient antibiotics at 1-year follow-up. CONCLUSIONS People should be alert to CNS infections caused by P. agglomerans which presented with relatively mild clinical symptoms at onset, especially for those who contucts relevant agricultural and forestry work. The CSF characterization of P. agglomerans meningitis is elevated multiple nuclei white blood cells, significantly reduced glucose content, and markedly increased protein level which may be related to the secondary spinal membrane adhesions.
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Affiliation(s)
- Honghao Li
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, China
| | - Jing Yu
- Department of Pathology and Pathophysiology, Shandong Medical College, Jinan City, China
| | - Ziling Zeng
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, China.
| | - Cuicui Liu
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, China
| | - Ye Zhang
- Department of Scientific Affairs, Hugobiotech Co., Ltd, Beijing, 100176, China
| | - Han Xia
- Department of Scientific Affairs, Hugobiotech Co., Ltd, Beijing, 100176, China
| | - Shougang Guo
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, China
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Shumnalieva R, Mileva N, Padjen I, Siliogkas P, Chervenkov L, Bakopoulou K, Kaouri IE, Vasilska A, Miteva D, Vassilev D, Velikova T. Management of Coronary Artery Diseases in Systemic Vasculitides: Complications and Strategies. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1574. [PMID: 39459361 PMCID: PMC11509434 DOI: 10.3390/medicina60101574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/13/2024] [Accepted: 09/20/2024] [Indexed: 10/28/2024]
Abstract
Coronary artery disease (CAD) presents a significant risk for patients with systemic vasculitides, a group of disorders characterized by the inflammation of blood vessels. In this review, we focus on the pathophysiological mechanisms, complications, and management strategies for CAD in systemic vasculitides. We highlight how the inflammatory processes inherent in vasculitis contribute to accelerated atherosclerosis and myocardial ischemia. Key strategies in managing CAD in this patient population include using medicine treatments to mitigate vascular inflammation while balancing the risk of promoting cardiovascular events and lifestyle modifications. Understanding the nuanced relationship between systemic vasculitides and CAD is crucial for improving patient outcomes and guiding therapeutic approaches.
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Affiliation(s)
- Russka Shumnalieva
- Department of Rheumatology, Clinic of Rheumatology, University Hospital St. Ivan Rilski, Urvich Str. 13, 1612 Sofia, Bulgaria;
- Faculty of Medicine, Medical University of Sofia, Urvich Str. 13, 1612 Sofia, Bulgaria
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
| | - Niya Mileva
- Cardiology Department, SHATC Medica Cor, Riga Str. 35, 7013 Ruse, Bulgaria;
| | - Ivan Padjen
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, University of Zagreb, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia;
| | - Periklis Siliogkas
- General Hospital of Athens Korgialeneio—Benakeio Hellenic Red Cross, Athanasaki 11, 11526 Athens, Greece;
| | - Lyubomir Chervenkov
- Department of Diagnostic Imaging, Medical University Plovdiv, Bul. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria; (L.C.); (A.V.)
- Research Complex for Translational Neuroscience, Medical University of Plovdiv, Bul. Vasil Aprilov 15A, 4002 Plovdiv, Bulgaria
| | - Konstantina Bakopoulou
- Faculty of Medicine, Medical University Sofia, Boulevard ‘Akademik Ivan Evstratiev Geshov’ 15, 1431 Sofia, Bulgaria; (K.B.); (I.E.K.)
| | - Issa El Kaouri
- Faculty of Medicine, Medical University Sofia, Boulevard ‘Akademik Ivan Evstratiev Geshov’ 15, 1431 Sofia, Bulgaria; (K.B.); (I.E.K.)
| | - Anna Vasilska
- Department of Diagnostic Imaging, Medical University Plovdiv, Bul. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria; (L.C.); (A.V.)
| | - Dimitrina Miteva
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
- Department of Genetics, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tzankov Str., 1164 Sofia, Bulgaria
| | - Dobrin Vassilev
- Ruse University Angel Kanchev, ul. “Studentska” 8, 7017 Ruse, Bulgaria;
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
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Li L, Teng J, Kou N, Yue Y, Wang H. ANCA-associated vasculitis and lung cancer: an immunological perspective. Clin Exp Med 2024; 24:208. [PMID: 39230721 PMCID: PMC11374858 DOI: 10.1007/s10238-024-01475-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 08/20/2024] [Indexed: 09/05/2024]
Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune disease that often involves the upper and lower respiratory tracts. In recent years, numerous studies have found a significant increase in the incidence of cancer among AAV patients, but the association between lung cancer and AAV remains inconclusive, with relatively low clinical attention. This review summarizes the current literature on the risk of lung cancer in patients with ANCA-associated vasculitis (AAV), detailing the potential mechanisms by which AAV may contribute to lung cancer, and further elucidates the inherent carcinogenic risks of immunosuppressants.There is a correlation between AAV and lung cancer, which is related to T cell senescence and damage, as well as the abnormal expression of cytokines such as IL-6 and IL-10. In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients.
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Affiliation(s)
- Longzhao Li
- Respiratory Disease Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.116 Cuiping West Road, Tongzhou District, 101121, Beijing, China
- Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Jun Teng
- Respiratory Disease Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.116 Cuiping West Road, Tongzhou District, 101121, Beijing, China
- Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Na Kou
- Respiratory Disease Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.116 Cuiping West Road, Tongzhou District, 101121, Beijing, China
| | - Yuan Yue
- Respiratory Disease Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.116 Cuiping West Road, Tongzhou District, 101121, Beijing, China
| | - HongWu Wang
- Respiratory Disease Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.116 Cuiping West Road, Tongzhou District, 101121, Beijing, China.
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Karacabeyli D, Lacaille D, Lu N, McCormick N, Xie H, Choi HK, Aviña-Zubieta JA. Mortality and major adverse cardiovascular events after glucagon-like peptide-1 receptor agonist initiation in patients with immune-mediated inflammatory diseases and type 2 diabetes: A population-based study. PLoS One 2024; 19:e0308533. [PMID: 39116084 PMCID: PMC11309412 DOI: 10.1371/journal.pone.0308533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 07/24/2024] [Indexed: 08/10/2024] Open
Abstract
OBJECTIVE To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes newly initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is). METHODS We performed a population-based cohort study using administrative health data from British Columbia. Patients with an IMID (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i between January 1, 2010, and December 31, 2021 were identified using ICD-9/10 codes. The primary outcome was all-cause mortality. Secondary outcomes included MACE and its components (i.e., cardiovascular death, myocardial infarction, and ischemic stroke). Cox proportional hazard regressions were used with propensity score overlap weighting. The analysis was repeated in age- and sex-matched adults without IMIDs. RESULTS We identified 10,855 adults with IMIDs and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1-RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.31-0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years. Rate of MACE was also lower with GLP-1-RA exposure (HR 0.66 [0.50-0.88], RD -10.5 [-20.4 to -0.8]). Effect sizes were similar in adults without IMIDs. CONCLUSION In patients with IMIDs and type 2 diabetes, GLP-1-RA exposure is associated with a lower risk of all-cause mortality and MACE compared to a cardioneutral active comparator.
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Affiliation(s)
- Derin Karacabeyli
- Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Arthritis Research Canada, Vancouver, British Columbia, Canada
| | - Diane Lacaille
- Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Arthritis Research Canada, Vancouver, British Columbia, Canada
| | - Na Lu
- Arthritis Research Canada, Vancouver, British Columbia, Canada
| | - Natalie McCormick
- Arthritis Research Canada, Vancouver, British Columbia, Canada
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| | - Hui Xie
- Arthritis Research Canada, Vancouver, British Columbia, Canada
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Hyon K. Choi
- Arthritis Research Canada, Vancouver, British Columbia, Canada
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| | - J. Antonio Aviña-Zubieta
- Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Arthritis Research Canada, Vancouver, British Columbia, Canada
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Tumba MC, Silva RL, Arevalo AB, Sattui SE. Current perspective on infections and mitigation strategies in primary systemic vasculitis. Curr Rheumatol Rep 2024; 26:279-289. [PMID: 38668813 DOI: 10.1007/s11926-024-01149-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2024] [Indexed: 07/05/2024]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize and evaluate most recent evidence on the epidemiology of infections and associated risk factors in patients with primary systemic vasculitides (PSV), as well as discuss mitigation strategies including the risk of antibiotic prophylaxis. RECENT FINDINGS Infections remain one of the leading causes of mortality in patients with PSV, with rates of severe infection ranging from 16 to 40% in different cohorts. Older age, frailty, renal and pulmonary involvement, and higher burden of comorbidities have been recognized as important patient-associated risk factors. Treatments including higher cumulative doses of glucocorticoids are associated with an increased risk of infections, and recent studies show the potential benefit of interventions such as reduced-dose glucocorticoid regimens. Existing mitigation strategies include screening, vaccination, and infection prophylaxis. The latter remains particularly important for Pneumocystis jirovecii pneumonia; however, the benefit-risk ratio seems to be less clear outside of induction phase (i.e., high dose of glucocorticoids) and optimal treatment duration remains less clear. Patients with PSV are at increased risk of infections, due to disease itself, comorbidities, and treatment side effects. Awareness of the timing and types of infection, as well as mitigation strategies are imperative to ensure treatment success and survival for patients.
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Affiliation(s)
- Manuel Carpio Tumba
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Raisa Lomanto Silva
- Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ana B Arevalo
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Massachusetts, Boston, MA, USA
| | - Sebastian E Sattui
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
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29
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Nygaard L, Polcwiartek C, Nelveg-Kristensen KE, Carlson N, Kristensen S, Torp-Pedersen C, Gregersen JW. Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study. Rheumatology (Oxford) 2024; 63:1313-1321. [PMID: 37481712 DOI: 10.1093/rheumatology/kead377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/30/2023] [Indexed: 07/24/2023] Open
Abstract
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.
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Affiliation(s)
- Louis Nygaard
- Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
- SLE and Vasculitis Clinic, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Christoffer Polcwiartek
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Nicholas Carlson
- Department of Nephrology, Copenhagen University Hospital, Copenhagen, Denmark
- Research Department, The Danish Heart Foundation, Copenhagen, Denmark
| | - Salome Kristensen
- SLE and Vasculitis Clinic, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Torp-Pedersen
- Department of Cardiology, North Zealand Hospital, Hillerød, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Jon Waarst Gregersen
- Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
- SLE and Vasculitis Clinic, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Falde SD, Fussner LA, Tazelaar HD, O'Brien EK, Lamprecht P, Konig MF, Specks U. Proteinase 3-specific antineutrophil cytoplasmic antibody-associated vasculitis. THE LANCET. RHEUMATOLOGY 2024; 6:e314-e327. [PMID: 38574742 DOI: 10.1016/s2665-9913(24)00035-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 01/13/2024] [Accepted: 02/06/2024] [Indexed: 04/06/2024]
Abstract
Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.
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Affiliation(s)
- Samuel D Falde
- Division of Pulmonary & Critical Care Medicine, Mayo Clinic Rochester, Rochester, MN, USA
| | - Lynn A Fussner
- Division of Pulmonary, Critical Care Medicine, and Sleep Medicine, Ohio State University, Columbus, OH, USA
| | - Henry D Tazelaar
- Department of Anatomic Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Erin K O'Brien
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic Rochester, Rochester, MN, USA
| | - Peter Lamprecht
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
| | - Maximilian F Konig
- Division of Rheumatology, Department of Medicine & Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ulrich Specks
- Division of Pulmonary & Critical Care Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
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Lee JH, Hong SH, Yu I, Chang MS, Park S, Lee SJ, Kim SH. Incidence, Prevalence, and Mortality of Eosinophilic Granulomatosis With Polyangiitis in Korea: A Nationwide Population-Based Study. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2024; 16:168-178. [PMID: 38528384 DOI: 10.4168/aair.2024.16.2.168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 09/07/2023] [Accepted: 10/18/2023] [Indexed: 03/27/2024]
Abstract
PURPOSE Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis with multiorgan involvement. The incidence and prevalence of EGPA vary geographically and ethnically. This study investigated the incidence, prevalence, and mortality of EGPA in a nationwide population-based cohort in Korea. METHODS This retrospective cohort study used data from the National Health Insurance database that covers almost all Korean residents. EGPA was identified using relevant diagnostic codes from 2007 to 2018. Newly diagnosed EGPA cases since 2007 and patients who visited outpatient clinics for EGPA at least three times were included. Age- and sex-adjusted standardized incidence and prevalence rates were analyzed. RESULTS A total of 843 patients with EGPA were identified. The mean annual standardized incidence between 2007 and 2018 was 1.2 (per 1,000,000 individuals). The incidence of EGPA has increased from 1.1 (per 1,000,000 individuals) in 2007 to 1.6 (per 1,000,000 individuals) in 2017. The standardized prevalence of EGPA has increased from 1.1(per 1,000,000 individuals) in 2007 to 11.2 (per 1,000,000 individuals) in 2018. The incidence and prevalence of EGPA were higher in women than in men. The standardized mortality rate was 1.61 (95% confidence interval [CI], 1.34-1.93) in total population, 1.59 (95% CI, 1.23-2.02) in males, and 1.63 (95% CI, 1.22-2.13) in females. CONCLUSIONS The incidence of EGPA has increased over the past decade. Incidence and prevalence rates were higher in females than in males. The overall mortality rate associated with EGPA was higher than that in the general population.
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Affiliation(s)
- Ji-Ho Lee
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Se Hwa Hong
- Department of Biostatistics, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Iseul Yu
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Min-Seok Chang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sunmin Park
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Seok Jeong Lee
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sang-Ha Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
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Kronbichler A, Bajema IM, Bruchfeld A, Mastroianni Kirsztajn G, Stone JH. Diagnosis and management of ANCA-associated vasculitis. Lancet 2024; 403:683-698. [PMID: 38368016 DOI: 10.1016/s0140-6736(23)01736-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/05/2023] [Accepted: 08/17/2023] [Indexed: 02/19/2024]
Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies.
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Affiliation(s)
- Andreas Kronbichler
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria; Department of Medicine, University of Cambridge, Cambridge, UK.
| | - Ingeborg M Bajema
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands
| | - Annette Bruchfeld
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden
| | | | - John H Stone
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Ahn SS, Heo SJ, Ha JW, Park YB, Lee SW. Clinical association of health-related quality of life and mortality in an antineutrophil cytoplasmic antibody-associated vasculitis cohort. Semin Arthritis Rheum 2024; 64:152353. [PMID: 38128176 DOI: 10.1016/j.semarthrit.2023.152353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/27/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVES To evaluate the association between health-related quality of life (HRQoL) and mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS We searched patients with AAV assessed for HRQoL at initial diagnosis using Short Form 36 (SF-36). Relationships between SF-36 physical component summary (PCS) and mental component summary (MCS) scales and variables were estimated using Pearson's correlation analysis. Contal's and O'Quigley's methods were used to determine optimal SF-36 PCS cut-off for predicting all-cause mortality. The Cox proportional hazards model and inverse probability of treatment weighting (IPTW) analysis were used to ascertain prognostic implications of SF-36 scales and mortality. RESULTS The median SF-36 PCS and MCS values of the 189 patients were 47.5 and 53.3, respectively, and 21 (11.1%) patients (microscopic polyangiitis [MPA], n=15; granulomatosis with polyangiitis [GPA], n=6) died during follow-up. SF-36 PCS was significantly but weakly associated with Birmingham Vasculitis Activity Score, Five-factor score, erythrocyte sedimentation rate (ESR), and C-reactive protein. However, SF-36 MCS was not associated with ESR. In the multivariable Cox analysis, a decrease of SF-36 PCS score by one unit indicated a higher death risk (hazard ratio [HR]: 1.030; 95% confidence interval [CI]: 1.007, 1.052; p=0.041), which was not for SF-36 MCS. IPTW analysis in a subgroup of MPA and GPA patients revealed increased patient mortality with SF-36 PCS <53.75 independently (HR: 3.249; 95% CI: 1.169, 9.033; p=0.024). CONCLUSION Poor baseline physical functioning associated with premature death in patients with MPA and GPA. HRQoL assessment during initial diagnosis may provide clinical insights for this population.
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Affiliation(s)
- Sung Soo Ahn
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Seok-Jae Heo
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jang Woo Ha
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Yong-Beom Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang-Won Lee
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Gisslander K, Rutherford M, Aslett L, Basu N, Dradin F, Hederman L, Hruskova Z, Kardaoui H, Lamprecht P, Lichołai S, Musial J, O'Sullivan D, Puechal X, Scott J, Segelmark M, Straka R, Terrier B, Tesar V, Tesi M, Vaglio A, Wandrei D, White A, Wójcik K, Yaman B, Little MA, Mohammad AJ. Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying. Ann Rheum Dis 2024; 83:112-120. [PMID: 37907255 PMCID: PMC10804071 DOI: 10.1136/ard-2023-224571] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/16/2023] [Indexed: 11/02/2023]
Abstract
OBJECTIVES This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
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Affiliation(s)
- Karl Gisslander
- Clinical Sciences, Rheumatology, Lund University, Lund, Sweden
| | | | - Louis Aslett
- Department of Mathematical Science, University of Durham, Durham, UK
| | - Neil Basu
- School of Infection and Immunity, University of Glasgow, Glasgow, UK
| | | | - Lucy Hederman
- ADAPT SFI Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
| | - Zdenka Hruskova
- Department of Nephrology, General University Hospital, Prague, Czech Republic
- First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Hicham Kardaoui
- National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France
- Université Paris Cité, Paris, France
| | - Peter Lamprecht
- Department of Rheumatology and Clinical Immunology, Universitat zu Lubeck, Lubeck, Germany
| | - Sabina Lichołai
- Division of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College, Krakow, Poland
| | - Jacek Musial
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Declan O'Sullivan
- ADAPT SFI Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
| | - Xavier Puechal
- National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France
- French Vasculitis Study Group, Paris, France
| | - Jennifer Scott
- ADAPT SFI Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
- Trinity Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Mårten Segelmark
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Endocrinology, Nephrology and Rheumatology, Skåne University Hospital, Lund, Sweden
| | - Richard Straka
- General University Hospital in Prague, Praha, Czech Republic
| | - Benjamin Terrier
- National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France
- French Vasculitis Study Group, Paris, France
| | - Vladimir Tesar
- Department of Nephrology, General University Hospital, Prague, Czech Republic
- First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Michelangelo Tesi
- Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Firenze, Italy
| | - Augusto Vaglio
- Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Firenze, Italy
| | - Dagmar Wandrei
- Clinical Trials Unit, Medical Center, University of Freiburg Faculty of Medicine, Freiburg, Germany
| | - Arthur White
- School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
| | - Krzysztof Wójcik
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Beyza Yaman
- ADAPT SFI Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
| | - Mark A Little
- ADAPT SFI Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland
- Trinity Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Aladdin J Mohammad
- Clinical Sciences, Rheumatology, Lund University, Lund, Sweden
- Department of Medicine, University of Cambridge, Cambridge, UK
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Martin-Gómez MA, Rodríguez Torres A, Espinosa Hernández M, Lopez Mendoza M, Sabio Sánchez JM, Martin Armada M, Martin Suarez I, Callejas Rubio JL, Castilla Castellano MM, Anglada Pintado JC, Barnosi Marín AC, Martinez Esteban MD, Castilla Guerra L, De Ramón Garrido E. Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain. HIPERTENSION Y RIESGO VASCULAR 2024; 41:5-16. [PMID: 37517951 DOI: 10.1016/j.hipert.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 06/02/2023] [Accepted: 06/05/2023] [Indexed: 08/01/2023]
Abstract
BACKGROUND Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.
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Affiliation(s)
| | | | | | | | - J M Sabio Sánchez
- Internal Medicine Autoimmune Unit, Virgen de las Nieves Hospital, Granada, Spain
| | | | - I Martin Suarez
- Internal Medicine, Juan Ramón Jiménez Hospital, Huelva, Spain
| | | | | | | | | | | | | | - E De Ramón Garrido
- Internal Medicine, Andalussian Society of Autoimmune Diseases (AADEA), Spain
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36
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Sayer M, Chapman GB, Thomas M, Dhaun N. Cardiovascular Disease in Anti-neutrophil Cytoplasm Antibody-Associated Vasculitis. Curr Rheumatol Rep 2024; 26:12-23. [PMID: 38015334 PMCID: PMC10776689 DOI: 10.1007/s11926-023-01123-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2023] [Indexed: 11/29/2023]
Abstract
PURPOSE OF REVIEW Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare, multisystem, autoimmune disease characterised by microvascular inflammation. Over the past 20 years, advances in immunological management have improved short-term patient outcomes. Longer-term patient outcomes remain poor with cardiovascular disease now the leading cause of death in AAV. Here, we examine the potential pathways that contribute to the increased risk of cardiovascular disease in AAV and the current evidence to manage this risk. RECENT FINDINGS The incidence of cardiovascular disease in AAV exceeds that expected by traditional risk factors alone, suggesting a contribution from disease-specific factors. Similarly, it is unclear how different immunosuppressive therapies contribute to and modify cardiovascular risk, and there is a paucity of data examining the efficacy of traditional cardioprotective medications in AAV. There is a lack of evidence-based cardiovascular risk assessment tools and cardioprotective therapies in patients with AAV which should be addressed to improve long-term outcomes.
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Affiliation(s)
- Matthew Sayer
- Edinburgh Kidney, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Gavin B Chapman
- Edinburgh Kidney, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Matthew Thomas
- Edinburgh Kidney, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Neeraj Dhaun
- Edinburgh Kidney, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
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Qi F, Hao J, Wei W. Impact of different ANCA serotypes on the long-term outcome of ANCA-associated vasculitis patients. Ann Med 2023; 55:2289614. [PMID: 38056010 PMCID: PMC10836254 DOI: 10.1080/07853890.2023.2289614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/21/2023] [Indexed: 12/08/2023] Open
Abstract
OBJECTIVES To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes. METHODS Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared. RESULTS In this study, the average follow-up was 46.4 months (range 0.3-188.4 months). One hundred and seventy-seven (79.0%) patients were MPO-ANCA-positive and 47 were PR3-ANCA-positive; the mean age of MPO-ANCA positive patients at diagnosis was elder than that of PR3-ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3-ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3-ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3-ANCA patients were 60.7% and 76.9%, while that of MPO-ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis. CONCLUSIONS The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.
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Affiliation(s)
- Fumin Qi
- Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jian Hao
- Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
| | - Wei Wei
- Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
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Pillay SS, Nune A, Manzo C, Barman B, Raza H. A case of anti-neutrophil cytoplasmic antibody-associated vasculitis masquerading as Sjögren syndrome. Int J Rheum Dis 2023; 26:2555-2558. [PMID: 37427846 DOI: 10.1111/1756-185x.14823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 06/02/2023] [Accepted: 06/26/2023] [Indexed: 07/11/2023]
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA) -positive vasculitis is a small-vessel vasculitis that affects multiple body systems. Salivary gland involvement in ANCA-associated vasculitis is rare. When present, it mimics infection or malignancy, which might lead to misdiagnosis. In this report, we describe a 72-year-old man who presented with parotid and submandibular gland pain and swelling in addition to dry mouth and eyes. He had bilateral non-tender parotid gland lumps and no lymphadenopathies. Laboratory tests were positive for ANCA, hematuria, and proteinuria but negative for Anti-Ro and -La. He was treated with corticosteroids and cyclophosphamide for acute kidney injury. Unfortunately, the patient died a few months later. This case report sheds light on a rare manifestation of salivary gland involvement in ANCA-associated vasculitis that mimics Sjögren syndrome and the challenges associated with its diagnosis and treatment.
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Affiliation(s)
| | - Arvind Nune
- Southport and Ormskirk NHS Trust, Southport, UK
| | - Ciro Manzo
- Rheumatologic Outpatient Clinic, Sant'Agnello, Italy
| | - Bhupen Barman
- Department of General Medicine, All India Institute of Medical Sciences (AIIMS), Guwahati, India
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Rajasekaran A, Rizk DV. Evolution of Therapy for ANCA-Associated Vasculitis with Kidney Involvement. KIDNEY360 2023; 4:1794-1805. [PMID: 37927005 PMCID: PMC10758519 DOI: 10.34067/kid.0000000000000289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023]
Abstract
ANCA-associated vasculitis (AAV) belongs to a group of small vessel systemic vasculitides characterized by granulomatous and neutrophilic inflammation of various tissues. Patients often have circulating autoantibodies targeting neutrophilic antigens. Although AAV was once associated with severe end-organ damage and extremely high mortality rates, the use of glucocorticoids and cyclophosphamide led to a paradigm change in its treatment. Over the past 20 years, significant progress in understanding the immunopathogenesis of AAV has enabled development of targeted immunotherapies, providing a much better prognosis for patients. This review describes the evolution of treatment of AAV, particularly for patients with kidney involvement.
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Affiliation(s)
- Arun Rajasekaran
- Division of Nephrology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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Sorin B, Iudici M, Guerry MJ, Samson M, Bielefeld P, Maillet T, Nouvier M, Karras A, Meyer L, Lavigne C, Régent A, Durel CA, Fabre M, Charles P, Raimbourg Q, Lanteri A, Pugnet G, Rivière F, Pineton de Chambrun M, Cacoub P, Le Guenno G, Jourdain P, Mekinian A, Paule R, Dion J, Legendre P, Cohen P, Guillevin L, Puéchal X, Terrier B. Induction failure in granulomatosis with polyangiitis: a nationwide case-control study of risk factors and outcomes. Rheumatology (Oxford) 2023; 62:3662-3671. [PMID: 36847447 DOI: 10.1093/rheumatology/kead098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 02/08/2023] [Accepted: 02/20/2023] [Indexed: 03/01/2023] Open
Abstract
OBJECTIVE To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. METHODS We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment. RESULTS We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone. CONCLUSION In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.
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Affiliation(s)
- Boris Sorin
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Michele Iudici
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
- Division of Rheumatology, Department of Internal Medicine and Department of Medicine, Faculty of Medicine, Geneva University Hospitals, Geneve, Switzerland
| | - Mary-Jane Guerry
- Department of Nephrology, Centre Hospitalier de Valenciennes, Valenciennes, France
| | - Maxime Samson
- Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, Dijon, France
| | - Philip Bielefeld
- Department of Nephrology and Systemic Diseases, Hôpital François Mitterrand, Dijon, France
| | - Thibault Maillet
- Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, Dijon, France
| | - Mathilde Nouvier
- Department of Nephrology, Centre Hospitalier Lyon Sud, Lyon, France
| | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, Paris, France
| | - Lara Meyer
- Department of Nephrology, Hôpital Européen Georges Pompidou, Paris, France
| | - Christian Lavigne
- Department of Internal Medicine-Clinical Immunology, Centre Hospitalier Universitaire d'Angers, Angers, France
| | - Alexis Régent
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Cécile-Audrey Durel
- Department of Internal Medicine, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Marc Fabre
- Department of Internal Medicine, Centre Hospitalier Pierre Oudot, Bourgouin, France
| | - Pierre Charles
- Department of Internal Medicine, Institut Mutualiste Montsouris, Paris, France
| | - Quentin Raimbourg
- Department of Nephrology, Hôpital Bichat Claude Bernard, Paris, France
| | - Aurélia Lanteri
- Department of Internal Medicine-Infectious Diseases, Centre Hospitalier d'Antibes, Antibes, France
| | - Grégory Pugnet
- Department of Internal Medicine and Clinical Immunology, Hôpital Rangueil, Toulouse, France
| | - Frédéric Rivière
- Department of Pneumology, Hôpital d'Instruction des Armées Percy, Clamart, France
| | | | - Patrice Cacoub
- Department of Internal Medicine and Clinical Immunology, Hôpital Pitié Salpêtrière, Paris, France
| | - Guillaume Le Guenno
- Department of Internal Medicine, Hôpital d'Estaing, Clermont-Ferrand, France
| | - Pierre Jourdain
- Department of Nephrology, Centre Hospitalier Universitaire de Limoges, Limoges, France
| | - Arsène Mekinian
- Department of Internal Medicine, Hôpital Saint-Antoine, Paris, France
| | - Romain Paule
- Department of Internal Medicine, Hôpital Foch, Suresnes, France
| | - Jérémie Dion
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Paul Legendre
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
- Department of Clinical Immunology, Centre Hospitalier du Mans, Le Mans, France
| | - Pascal Cohen
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Loïc Guillevin
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Xavier Puéchal
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Benjamin Terrier
- Department of Internal Medicine, Hôpital Cochin, Paris, France
- National Reference Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
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Hanberg JS, Cook C, Fu X, Choi HK, Zhang Y, Wallace ZS. Longitudinal Patterns of Renal Function in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken) 2023; 75:2190-2198. [PMID: 36856264 PMCID: PMC10885164 DOI: 10.1002/acr.25100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 12/19/2022] [Accepted: 02/07/2023] [Indexed: 03/02/2023]
Abstract
OBJECTIVE A spectrum of chronic kidney disease (CKD) and end-stage renal disease (ESRD) may occur in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The longitudinal trajectory of renal function in AAV is poorly understood. METHODS Patients with ≥2 creatinine measurements, including at baseline (±30 days of treatment initiation), were included from the Mass General Brigham AAV Cohort. We calculated estimated glomerular filtration rate (eGFR). We incorporated longitudinal changes in eGFR into a group-based trajectory model to identify patients with similar patterns of change in renal function. The chi-square test and the Kruskal-Wallis test were used to evaluate differences between groups in categorical variables and non-normally distributed continuous variables, respectively. RESULTS In 255 AAV patients, we identified 4 renal trajectory groups: rapid decline (n = 20), impaired (n = 82), preserved (n = 129), and recovery (n = 24). The rapid decline and impaired groups had greater baseline comorbidity (P = 0.01) and lower prevasculitis eGFR (P = 0.02). Clinically significant CKD (eGFR <60 ml/minute/1.73 m2 ) persisted over 5 years in >75% of the impaired group, compared to <40% of patients in the preserved group (P < 0.001). ESRD occurred most frequently in the rapid decline (100%), followed by the impaired and preserved groups (7% each). Baseline AAV renal involvement was present prior to 95% of ESRD. However, ESRD etiology varied, with 90% of rapid-onset ESRD attributed to vasculitis, versus 17-44% in impaired or preserved groups (P = 0.001). CONCLUSION We identified 4 longitudinal patterns of renal function after AAV diagnosis. Our findings highlight the burden of CKD in AAV and provide a framework for future research into personalized care in this vulnerable population.
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Affiliation(s)
| | | | | | - Hyon K. Choi
- Massachusetts General Hospital and Harvard Medical School, Boston
| | - Yuqing Zhang
- Massachusetts General Hospital and Harvard Medical School, Boston
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42
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Held M, Sestan M, Kifer N, Jelusic M. Cerebrovascular involvement in systemic childhood vasculitides. Clin Rheumatol 2023; 42:2733-2746. [PMID: 36884156 DOI: 10.1007/s10067-023-06552-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 02/02/2023] [Accepted: 02/15/2023] [Indexed: 03/09/2023]
Abstract
Pediatric vasculitides sometimes involve central nervous system (CNS). The manifestations are diverse, ranging from headache, seizures, vertigo, ataxia, behavioral changes, neuropsychiatric symptoms, consciousness disorders, and even cerebrovascular (CV) accidents that may lead to irreversible impairment and even death. Stroke, on the other hand despite the great progress in prevention and treatment, is still one of the leading causes of morbidity and mortality in the general population. The aim of this article was to summarize CNS manifestations and CV issues observed in primary pediatric vasculitides and the current knowledge of etiology and CV risk factors, preventive strategies, and therapeutic options in this target patient population. Pathophysiological links reveal similar immunological mechanisms involved in both pediatric vasculitides and CV events with endothelial injury and damage being the central point. From the clinical point of view, CV events in pediatric vasculitides were associated with increased morbidity and poor prognosis. If damage has already occurred, the therapeutic approach consists of good management of the vasculitis itself, antiplatelet and anticoagulation therapy, and early rehabilitation. Risk factors for acquiring cerebrovascular disease (CVD) and stroke, particularly hypertension and early atherosclerotic changes, already begin in childhood, with vessel wall inflammation contributing itself, once more emphasizing that appropriate preventive measures are certainly necessary in pediatric vasculitis population to improve their long-term outcome.
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Affiliation(s)
- Martina Held
- Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Mario Sestan
- Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Nastasia Kifer
- Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Marija Jelusic
- Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
- Division of Clinical Immunology, Rheumatology and Allergology, Centre of Reference for Paediatric and Adolescent Rheumatology of Ministry of Health of the Republic Croatia, University Hospital Centre Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia.
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Wallace ZS, Fu X, Cook C, Ahola C, Williams Z, Doliner B, Hanberg JS, Stone JH, Zhang Y, Choi HK. Comparative Effectiveness of Rituximab- Versus Cyclophosphamide-Based Remission Induction Strategies in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the Risk of Kidney Failure and Mortality. Arthritis Rheumatol 2023; 75:1599-1607. [PMID: 37011036 PMCID: PMC10523845 DOI: 10.1002/art.42515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 03/23/2023] [Accepted: 03/31/2023] [Indexed: 04/04/2023]
Abstract
OBJECTIVE To compare rituximab- versus cyclophosphamide-based remission induction strategies for the long-term risks of kidney failure and death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in a real-world cohort. METHODS We performed a cohort study using the Mass General Brigham AAV Cohort, which includes proteinase 3-ANCA+ and myeloperoxidase (MPO)-ANCA+ AAV patients diagnosed from January 1, 2002 to December 31, 2019. We included cases in which the initial remission induction strategy was based either on rituximab or cyclophosphamide. The primary outcome was the composite outcome of kidney failure or death. We used multivariable Cox proportional hazards models and propensity score-matched analyses to assess the association of rituximab- versus cyclophosphamide-based treatment strategies with the composite outcome of kidney failure or death. RESULTS Of 595 included patients, 352 patients (~60%) received rituximab-based and 243 patients (~40%) received cyclophosphamide-based regimens. The mean age was 61 years, 58% of patients were female, 70% of patients were MPO-ANCA+, and 69% of patients had renal involvement (median estimated glomerular filtration rate 37.3 ml/minute/1.73 m2 ). There were 133 events at 5 years, and the incidence rates in rituximab- and cyclophosphamide-based regimens were 6.8 and 6.1 per 100 person-years, respectively. The risk of kidney failure or death was similar in both groups in multivariable-adjusted analyses (hazard ratio [HR] 1.03 [95% confidence interval (95% CI) 0.55-1.93]) and in propensity score-matched analyses (HR 1.05 [95% CI 0.55-1.99]) at 5 years. Our findings were similar when outcomes were assessed at 1 and 2 years as well as in subgroups stratified according to renal involvement and severity as well as major organ involvement. CONCLUSION Rituximab- and cyclophosphamide-based remission induction strategies for AAV are associated with similar risks of kidney failure and death.
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Affiliation(s)
- Zachary S. Wallace
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Xiaoqing Fu
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Claire Cook
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Catherine Ahola
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Zachary Williams
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Brett Doliner
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | | | - John H. Stone
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Yuqing Zhang
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Hyon K. Choi
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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Poledniczek M, Neumayer C, Kopp CW, Schlager O, Gremmel T, Jozkowicz A, Gschwandtner ME, Koppensteiner R, Wadowski PP. Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease-Pathophysiology and Translational Therapeutic Approaches. Biomedicines 2023; 11:2284. [PMID: 37626780 PMCID: PMC10452462 DOI: 10.3390/biomedicines11082284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/10/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.
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Affiliation(s)
- Michael Poledniczek
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
| | - Christoph Neumayer
- Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria;
| | - Christoph W. Kopp
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
| | - Oliver Schlager
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
| | - Thomas Gremmel
- Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, 2130 Mistelbach, Austria;
- Institute of Cardiovascular Pharmacotherapy and Interventional Cardiology, Karl Landsteiner Society, 3100 St. Pölten, Austria
| | - Alicja Jozkowicz
- Department of Medical Biotechnology, Faculty of Biophysics, Biochemistry and Biotechnology, Jagiellonian University, 31-007 Krakow, Poland;
| | - Michael E. Gschwandtner
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
| | - Renate Koppensteiner
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
| | - Patricia P. Wadowski
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (M.P.); (C.W.K.); (O.S.); (M.E.G.); (R.K.)
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45
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Odler B, Windpessl M, Eller K, Säemann MD, Lhotta K, Neumann I, Öberseder G, Duftner C, Dejaco C, Rudnicki M, Gauckler P, Hintenberger R, Zwerina J, Thiel J, Kronbichler A. [Diagnosis and therapy of granulomatosis with polyangiitis and microscopic polyangiitis-2023: consensus of the Austrian society of nephrology (ÖGN) and Austrian society of rheumatology (ÖGR)]. Wien Klin Wochenschr 2023; 135:656-674. [PMID: 37728651 PMCID: PMC10511611 DOI: 10.1007/s00508-023-02262-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2023] [Indexed: 09/21/2023]
Abstract
ANCA-associated vasculitides (AAV) are rare, complex systemic diseases that are often difficult to diagnose, because of unspecific clinical symptoms at presentation. However, the clinical course may be very dramatic and even life-threatening, necessitating prompt diagnosis and treatment.Therefore, it is important to increase disease awareness among physicians and support colleagues who are not confronted with these rare diseases on a regular basis. Here, the Austrian Society of Nephrology (ÖGN) and the Austrian Society of Rheumatology (ÖGR) provide a joint consensus on how to best diagnose and manage patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
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Affiliation(s)
- Balazs Odler
- Klinische Abteilung für Nephrologie, Abteilung für Innere Medizin III (Nephrologie, Dialyse und Hypertensiologie), Medizinische Universität Graz, Graz, Österreich
| | - Martin Windpessl
- Abteilung für Innere Medizin IV, Klinikum Wels-Grieskirchen, Wels, Österreich
- Medizinische Fakultät, JKU, Linz, Österreich
| | - Kathrin Eller
- Klinische Abteilung für Nephrologie, Abteilung für Innere Medizin III (Nephrologie, Dialyse und Hypertensiologie), Medizinische Universität Graz, Graz, Österreich
| | - Marcus D Säemann
- 6. Medizinische Abteilung mit Nephrologie & Dialyse, Klinik Ottakring, Wien, Österreich
- Medizinische Fakultät, SFU, Wien, Österreich
| | - Karl Lhotta
- Abteilung für Innere Medizin III (Nephrologie, Dialyse und Hypertensiologie), Akademisches Lehrkrankenhaus Feldkirch, Feldkirch, Österreich
| | - Irmgard Neumann
- Vasculitis.at, Wien, Österreich
- Immunologiezentrum Zürich (IZZ), Zürich, Schweiz
| | | | - Christina Duftner
- Department Innere Medizin II, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | | | - Michael Rudnicki
- Department Innere Medizin IV (Nephrologie und Hypertensiologie), Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Philipp Gauckler
- Department Innere Medizin IV (Nephrologie und Hypertensiologie), Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Rainer Hintenberger
- Abteilung Innere Medizin 2 (Gastroenterologie und Hepatologie, Endokrinologie und Stoffwechsel, Nephrologie, Rheumatologie), JKU, Linz, Österreich
| | - Jochen Zwerina
- 1. Medizinische Abteilung, Hanusch Krankenhaus, Wien, Österreich
| | - Jens Thiel
- Klinische Abteilung für Rheumatologie und Immunologie, Bereich Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Andreas Kronbichler
- Department Innere Medizin IV (Nephrologie und Hypertensiologie), Medizinische Universität Innsbruck, Innsbruck, Österreich.
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Gao R, Wu Z, Xu X, Pu J, Pan S, Zhang Y, Zhuang S, Yang L, Liang Y, Song J, Tang J, Wang X. Predictors of poor prognosis in ANCA-associated vasculitis (AAV): a single-center prospective study of inpatients in China. Clin Exp Med 2023; 23:1331-1343. [PMID: 36244021 PMCID: PMC10390347 DOI: 10.1007/s10238-022-00915-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 10/06/2022] [Indexed: 12/01/2022]
Abstract
To identify potential predictors by assessing adverse outcomes in ANCA-associated vasculitis (AAV) patients. Eighty-nine untreated AAV patients were followed up to January 31, 2022, death, or loss of follow-up. Clinical characteristics, laboratory tests, treatment, and progress were collected, and disease activity was evaluated via Birmingham Vasculitis Activity Score (BVAS). We determined risk factors of high-risk events, defined as developing tumors, renal replacement therapy (RRT), and death. Patients and renal survivals were computed by the Kaplan-Meier curve analysis. Cox regression analysis was performed for assessing variables for predicting death. During 267 person-years follow-up, 46 patients occurred high-risk events, including 20 patients receiving RRT, 12 patients developing tumors, and 29 patients who died mostly from organ failure and infection. Decreased estimated glomerular filtration rate (eGFR) (P < 0.001) and complement 3 levels (P = 0.019) were associated with high-risk events. Patients with lower serum potassium tended to develop tumors (P = 0.033); with higher BVAS (HR = 1.290, 95%CI 1.075-1.549, P = 0.006) and lower eGFR (HR = 0.782, 95%CI 0.680-0.901, P = 0.001) were more likely to undergo RRT. Patients with cardio and renal involvement exhibited a lower frequency of renal survival and all-cause mortality. Through multivariate COX analysis, age (HR = 1.016, 95%CI 1.016-1.105, P = 0.006) and eGFR (HR = 0.982, 95%CI 0.968-0.997, P = 0.018) predicted death in AAV, separately. The BVAS and eGFR could be a great prognosticator for RRT, while age and eGFR can independently predict the death. Serum potassium level and immunoglobulins should be focused on their predictor value in development of cancer and renal outcomes in AAV patients.
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Affiliation(s)
- Ronglin Gao
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Zhenzhen Wu
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Xianghuai Xu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Jincheng Pu
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Shengnan Pan
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Youwei Zhang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Shuqi Zhuang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Lufei Yang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Yuanyuan Liang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Jiamin Song
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China
| | - Jianping Tang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China.
| | - Xuan Wang
- Department of Rheumatology and Immunology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China.
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Tabakovic D, Smith R, Jayne D, Mohammad AJ. High risk of stroke in ANCA-associated vasculitis-a population-based study. Rheumatology (Oxford) 2023; 62:2806-2812. [PMID: 36440920 PMCID: PMC10393431 DOI: 10.1093/rheumatology/keac669] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 11/19/2022] [Indexed: 08/03/2023] Open
Abstract
OBJECTIVE To determine the incidence rate, predictors and outcome of stroke in a population-based cohort of individuals with ANCA-associated vasculitis (AAV). METHODS The study included 325 patients diagnosed with AAV from 1997 through 2016 in a defined geographic area of Sweden. Patients who suffered a stroke were identified from Riksstroke, a national Swedish stroke register established in 1994, and the Skåne Healthcare Register (SHR), which includes data for all inhabitants of Skåne since 1998. Case record review was carried out to confirm the diagnosis of stroke in AAV patients identified in the SHR. The incidence rate of stroke was calculated per 1000 person-years of follow-up. Using data from the Swedish general population, the standardized incidence ratio (SIR) of stroke was estimated. Cox regression analysis was utilized to investigate survival and predictors of stroke. RESULTS Twenty-five subjects (8%) suffered a stroke during 2206 person-years of follow-up. The incidence rate of stroke in AAV was 11.3/1000 person-years (95% CI 6.9, 15.8). Patients with AAV showed an increased risk of stroke compared with the general population [SIR 1.85 (95% CI 1.27, 2.59)], with a greater risk for those <65 years of age [SIR 3.19 (95% CI 1.53, 5.88)]. Higher platelet count at AAV diagnosis was an independent predictor of stroke [hazard ratio 1.14 (95% CI 1.00, 1.29)]. There were no differences in survival or other outcome measures between AAV patients with and without stroke. CONCLUSIONS The incidence rate of stroke in AAV is higher than in the general population. High platelet count at AAV diagnosis was associated with an increased risk of stroke.
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Affiliation(s)
- Dennis Tabakovic
- Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital, Lund, Sweden
| | - Rona Smith
- Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - David Jayne
- Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Aladdin J Mohammad
- Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden
- Department of Rheumatology, Skåne University Hospital, Lund, Sweden
- Department of Medicine, University of Cambridge, Cambridge, UK
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Ahn SS, Pyo JY, Song JJ, Park YB, Lee SW. A prognostic immune nutritional index can predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Ther Adv Musculoskelet Dis 2023; 15:1759720X231188818. [PMID: 37529333 PMCID: PMC10387778 DOI: 10.1177/1759720x231188818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 06/28/2023] [Indexed: 08/03/2023] Open
Abstract
Background Studies have proposed that nutritional and immune-related markers are relevant with patient outcomes of various medical conditions and could be a useful indicator of patient prognostication. Objectives This study investigated whether a prognostic immune nutritional index (PINI) at diagnosis could predict adverse clinical outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Design A retrospective, single-centre observational cohort analysis of patients with AAV. Methods All-cause mortality and end-stage renal disease (ESRD) were investigated outcomes during the observation period. PINI was calculated by serum albumin (g/mL) × 0.9 - monocyte count (/mm3) × 0.0007, and the optimal cut-off of PINI was obtained using a Youden index-based bootstrapping method. Cox hazard analyses were performed to identify independent predictors of patient outcomes. Results Of the 250 eligible patients, the median age of patients was 60.0 years, and 34.0% were men. During the disease course, 33 (13.2%) died and 42 (16.8%) developed ESRD, respectively. The ideal PINI cut-offs for all-cause mortality and ESRD were set as ⩽2.47 and ⩽3.12 (sensitivity and specificity of 75.1% and 60.6% for mortality and 46.2% and 78.6% for ESRD). AAV patients with PINI ⩽2.47 and those with PINI ⩽3.12 exhibited significantly higher rates for all-cause mortality and ESRD compared to those with PINI >2.47 and >3.12. In the multivariable Cox analysis, PINI ⩽2.47 (hazard ratio [HR]: 3.173, 95% confidence interval [CI]: 1.129, 8.916, p = 0.029) was independently associated with all-cause patient mortality; however, PINI ⩽3.12 was not independently associated with ESRD (HR: 1.097, 95% CI: 0.419, 2.870, p = 0.850). Conclusion Findings from this study demonstrated PINI could predict all-cause patient mortality in AAV, and a higher clinical attention is warranted in those with PINI ⩽2.47 at initial diagnosis.
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Affiliation(s)
- Sung Soo Ahn
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jung Yoon Pyo
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jason Jungsik Song
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong-Beom Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang-Won Lee
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
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Baqir M, Singam NS, DuBrock H. Pulmonary hypertension in ANCA-associated vasculitis: a retrospective analysis. SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2023; 40:e2023020. [PMID: 37382075 PMCID: PMC10494752 DOI: 10.36141/svdld.v40i2.13631] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 05/27/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND Little is known about pulmonary hypertension (PH) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES The aims of this retrospective study, in which echocardiography was used for detection of PH, were to identify the potential causes of PH in AAV and to analyze the risk factors for mortality. METHODS We performed a retrospective descriptive review of 97 patients who had AAV with PH at our institution from January 1, 1997, through December 31, 2015. These patients with PH were compared with 558 patients who had AAV without PH. Demographic and clinical data were abstracted from electronic health records. RESULTS Among the patients who had PH, 61% were men; mean (SD) age was 70.5 (14.1) years at the time of PH diagnosis. The majority of patients with PH (73.2%) had more than 1 potential cause of PH, with left heart disease and chronic lung disease being the most common causes. Older age, male sex, smoking history, and kidney involvement were associated with the presence of PH. PH was associated with an increased risk of death (hazard ratio, 3.15; 95% CI, 2.37-4.18). On multivariate analysis, PH, age, smoking status, and kidney involvement were independent risk factors for death. Median survival after the diagnosis of PH was 25.9 months (95% CI, 12.2-49.9). CONCLUSIONS PH in AAV is often multifactorial, is commonly associated with left heart disease, and is associated with a poor prognosis.
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Affiliation(s)
- Misbah Baqir
- Pulmonary Medicine Department, Mayo Clinic Rochester MN USA.
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50
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Ha JW, Ahn SS, Song JJ, Park YB, Lee SW. Total Globulin Fraction at Diagnosis Could Forecast All-Cause Mortality during the Disease Course in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. J Clin Med 2023; 12:4170. [PMID: 37373863 DOI: 10.3390/jcm12124170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/12/2023] [Accepted: 06/19/2023] [Indexed: 06/29/2023] Open
Abstract
Total globulin fraction (TGF) is calculated by subtracting serum albumin levels from serum total protein levels. The present study examined whether TGF at diagnosis could forecast all-cause mortality during the disease course in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The present study included 283 patients with AAV. The variables at AAV diagnosis such as demographic data, AAV-specific data including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and laboratory data including ANCA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were collected. The number of deceased patients during the follow-up duration based on all-cause mortality was counted. The median age of the 283 AAV patients was 60 years, and 35.7% were men. ANCAs were detected in 228 patients, and the median TGF was 2.9. A total of 39 patients (13.8%) died within a median follow-up duration of 46.9 months. TGF at AAV diagnosis was significantly correlated with ESR and CRP rather than AAV activity. Patients with ANCA positivity exhibited a significantly higher median TGF at AAV diagnosis than those without. Patients with TGF ≥ 3.1 g/dL at AAV diagnosis exhibited a significantly lower cumulative survival rate than those without. Furthermore, in the multivariable Cox hazards model analysis, TGF ≥ 3.1 g/dL (hazard ratio 2.611) was independently associated with all-cause mortality, along with age, male sex, and body mass index. The present study is the first to demonstrate that TGF at AAV diagnosis can forecast all-cause mortality during the disease course in AAV patients.
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Affiliation(s)
- Jang-Woo Ha
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Sung-Soo Ahn
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jason-Jungsik Song
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Yong-Beom Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Sang-Won Lee
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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