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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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Fouka E, Drakopanagiotakis F, Steiropoulos P. Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome. Int J Mol Sci 2024; 25:5278. [PMID: 38791316 PMCID: PMC11121030 DOI: 10.3390/ijms25105278] [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: 03/06/2024] [Revised: 05/09/2024] [Accepted: 05/11/2024] [Indexed: 05/26/2024] Open
Abstract
Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.
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Affiliation(s)
- Evangelia Fouka
- Department of Respiratory Medicine, General Hospital G. Papanikolaou, Medical School, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece;
| | - Fotios Drakopanagiotakis
- Department of Respiratory Medicine, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Paschalis Steiropoulos
- Department of Respiratory Medicine, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
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Bonner RW, Moreno V, Jain K. Infection-Associated Glomerulonephritis. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:246-254. [PMID: 39004464 DOI: 10.1053/j.akdh.2024.01.001] [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: 07/06/2023] [Revised: 12/20/2023] [Accepted: 01/02/2024] [Indexed: 07/16/2024]
Abstract
The nephritic syndrome has been associated with a wide variety of infections, spanning many organisms and myriad clinical presentations. Infection-associated glomerulonephritis is challenging to diagnose given the many confounding factors linking kidney injury to infection; however, urine microscopy can assist in identifying abnormal cellular elements suggestive of glomerulonephritis. Kidney biopsy remains the gold standard for diagnosing the underlying pathologic lesion. Treatment of infection-associated glomerulonephritis centers around aggressive and complete treatment of the underlying infectious driver. It is often hard to know exactly when immunosuppression may be required in addition to treating the infection.
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Affiliation(s)
- Ryan W Bonner
- Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Vanessa Moreno
- Division of Nephropathology, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Koyal Jain
- Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
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Lu H, Cui Z, Zhou XJ, Yang Y, Han XN, Li XH, Zhou FD, Zhao MH. Proteinase‑3‑antineutrophil cytoplasmic antibody‑associated vasculitis secondary to subacute infective endocarditis: A case report. Exp Ther Med 2024; 27:216. [PMID: 38590565 PMCID: PMC11000458 DOI: 10.3892/etm.2024.12504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 02/02/2024] [Indexed: 04/10/2024] Open
Abstract
A 58-year-old male patient was admitted to Peking University First Hospital (Beijing, China) due to recurrent hematuria, proteinuria and kidney dysfunction. The patient was positive for proteinase-3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). Pathology of the kidney showed focal proliferative necrotizing glomerulonephritis with crescent formation and immune complex-mediated glomerulonephritis. The patient was diagnosed with PR3-ANCA-associated vasculitis (AAV), received intensive immunosuppressive therapy and experienced two relapses within 1 year. After admission, aortic valve vegetation was observed via echocardiography. The patient subsequently received antibiotic treatment and valve replacement, and achieved complete remission of kidney and cardiac function. The present case emphasized the importance of identifying secondary reasons for ANCA formation, especially infective endocarditis in patients with PR3-AAV.
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Affiliation(s)
- Hui Lu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, P.R. China
- Institute of Nephrology, Peking University, Beijing 100034, P.R. China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, P.R. China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100034, P.R. China
| | - Zhao Cui
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, P.R. China
- Institute of Nephrology, Peking University, Beijing 100034, P.R. China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, P.R. China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100034, P.R. China
| | - Xu-Jie Zhou
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, P.R. China
- Institute of Nephrology, Peking University, Beijing 100034, P.R. China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, P.R. China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100034, P.R. China
| | - Ying Yang
- Department of Cardiology, Peking University First Hospital, Beijing 100034, P.R. China
| | - Xiao-Ning Han
- Department of Cardiology, Peking University First Hospital, Beijing 100034, P.R. China
| | - Xi-Hui Li
- Department of Cardiac Surgery, Peking University First Hospital, Beijing 100034, P.R. China
| | - Fu-De Zhou
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, P.R. China
- Institute of Nephrology, Peking University, Beijing 100034, P.R. China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, P.R. China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100034, P.R. China
| | - Ming-Hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, P.R. China
- Institute of Nephrology, Peking University, Beijing 100034, P.R. China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, P.R. China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100034, P.R. China
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Agur Cohen D, Braun E. Unusual subacute endocarditis following herpes zoster infection. a case report. Fam Pract 2024; 41:214-218. [PMID: 38069742 DOI: 10.1093/fampra/cmad113] [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] [Indexed: 04/16/2024] Open
Abstract
OBJECTIVE This paper presents a rare case of subacute bacterial endocarditis (SBE) following a herpes zoster (HZ) episode, with no prior records found in the existing literature. PATIENT INFORMATION Specifically, we describe a case of a 76-year-old female whose diagnosis of SBE was hindered by the concurrent manifestation of HZ symptoms, which had emerged 3 weeks before the onset of SBE indicators. FOLLOW-UP AND OUTCOMES This delay in diagnosis resulted in profound complications, including a cerebrovascular accident and significant mitral valve destruction. DISCUSSION HZ episodes have not conventionally been linked in the medical literature to the occurrence of SBE. Nonetheless, it is noteworthy that HZ infections have been associated with the development of other consequential bacterial infections, such as pneumonia and necrotizing fasciitis.This case underscores the necessity for medical practitioners to recognize the possibility of HZ symptoms obscuring indications of critical underlying conditions and infections. The implications of this report highlight the significance of maintaining heightened vigilance for signs of other severe infections when managing patients presenting with HZ symptoms.
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Affiliation(s)
- Dikla Agur Cohen
- The Rappaport Faculty of Medicine, Technion, Haifa, Israel
- Family Physician Department, Haifa and West Galilee District, Clalit Health Service, Haifa, Israel
| | - Eyal Braun
- The Rappaport Faculty of Medicine, Technion, Haifa, Israel
- Division of Internal Medicine, Rambam Health Care Campus, Haifa, Israel
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Koster MJ, Guarda M, Ghaffar U, Warrington KJ. Rheumatic masqueraders: mimics of primary vasculitis - a case-based review. Expert Rev Clin Immunol 2024; 20:83-95. [PMID: 37837326 DOI: 10.1080/1744666x.2023.2270774] [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: 03/31/2023] [Accepted: 10/10/2023] [Indexed: 10/16/2023]
Abstract
INTRODUCTION Vasculitis conditions are often serious and sometimes fatal diseases, therefore it is paramount to diagnose correctly and treat appropriately. Mimics of primary vasculitis can include either non-inflammatory syndromes or secondary vasculitis where the underlying etiology of the vasculitis is being driven by infection, malignancy, drug-effect or other. AREAS COVERED This review comprises six individual cases of vasculitis mimics. Each case is presented and the clinical, radiographic, and histological features that distinguish the case from primary vasculitis are highlighted. Key mimics in large, medium and small vessel vasculitis are outlined. EXPERT OPINION The diagnosis of vasculitis requires a comprehensive assessment of clinical, radiographic, and histologic features. Clinicians should be familiar with mimics of primary vasculitis conditions. In the case of non-inflammatory mimics, it is important to differentiate from primary vasculitides in order to avoid unnecessary and potentially harmful immunosuppression. For cases of secondary vasculitis, identification of the correct etiologic cause is critical because treatment of the underlying stimulus is necessary for successful management and outcomes.
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Affiliation(s)
- Matthew J Koster
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Max Guarda
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Umar Ghaffar
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Kenneth J Warrington
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
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Leleux C, Zerbib Y, Pommerolle P, Da Rocha A, Serpier M, Caillard P. Rare manifestations of cryoglobulinemic vasculitis: a case report. Front Immunol 2023; 14:1271584. [PMID: 37901234 PMCID: PMC10611471 DOI: 10.3389/fimmu.2023.1271584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 09/27/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often accompanied by nonspecific cutaneous, articular, neurological, and renal manifestations. Diagnosing cryoglobulinemia through biological testing can be time-consuming and sometimes yields negative results, making diagnosis challenging. There are also other potentially life-threatening complications that can significantly impact prognosis and delay urgent treatment, including digestive manifestations and heart failure. Case presentation We report the case of a 60-year-old male patient with a medical history of rheumatoid arthritis. He was admitted to the Nephrology Department for investigation of necrotic vascular purpura, acute kidney injury, and pancytopenia. Laboratory tests revealed consumption of the C3 and C4 complement fractions and the presence of mixed-type III cryoglobulinemia. Despite the initiation of the treatment, the patient rapidly developed multiple severe organ failures, including renal, cardiac, respiratory, and finally digestive complications. Acute colic ischemia led to emergency surgery and the patient was transferred to the Intensive Care Unit. Despite surgical intervention and hemodynamic support, the patient experienced multi-visceral organ failure and died two hours after admission. Discussion Mixed cryoglobulinemia vasculitis may result in rare cases of acute and life-threatening organ damage, such as cardiac or respiratory failure with pulmonary hemorrhage, gastrointestinal ischemia, and neurological disorders. These severe manifestations are associated with a poor prognosis and it is crucial to promptly initiate an aggressive therapeutic strategy.
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Affiliation(s)
- Charlotte Leleux
- Department of Internal Medicine, Amiens University Hospital, Amiens, France
| | - Yoann Zerbib
- Department of Intensive Care Unit, University of Picardie Jules Verne, Amiens University Hospital, Amiens, France
| | - Pierre Pommerolle
- Department of Nephrology, Dialysis, and Transplantation, University of Picardie Jules Verne, Amiens University Hospital, Amiens, France
| | - Audrey Da Rocha
- Department of Hematology, Amiens University Hospital, Amiens, France
| | - Marine Serpier
- Department of Internal Medicine, Amiens University Hospital, Amiens, France
| | - Pauline Caillard
- Department of Nephrology, Dialysis, and Transplantation, University of Picardie Jules Verne, Amiens University Hospital, Amiens, France
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Yang X, Jiao C, Liu X, Zhang Y, Zhou H, Wang Y. Coexistence of cryoglobulinemia and ANCA-associated vasculitis in a chronic brucellosis patient -a case report and literature review. BMC Infect Dis 2023; 23:272. [PMID: 37131122 PMCID: PMC10152744 DOI: 10.1186/s12879-023-08232-w] [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: 12/05/2022] [Accepted: 04/06/2023] [Indexed: 05/04/2023] Open
Abstract
BACKGROUND The renal involvement of brucellosis is not common. Here we reported a rare case of chronic brucellosis accompanied by nephritic syndrome, acute kidney injury, the coexistence of cryoglobulinemia and antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) superimposed on iliac aortic stent implantation. The diagnosis and treatment of the case are instructive. CASE PRESENTATION A 49-year-old man with hypertension and iliac aortic stent implantation was admitted for unexplained renal failure with signs of nephritic syndrome, congestive heart failure, moderate anemia and livedoid change in the left sole with pain. His past history included chronic brucellosis and he just underwent the recurrence and completed the 6 weeks of antibiotics treatment. He demonstrated positive cytoplasmic/proteinase 3 ANCA, mixed type cryoglobulinemia and decreased C3. The kidney biopsy revealed endocapillary proliferative glomerulonephritis with a small amount of crescent formation. Immunofluorescence staining revealed only C3-positive staining. In accordance with clinical and laboratory findings, post-infective acute glomerulonephritis superimposed with AAV was diagnosed. The patient was treated with corticosteroids and antibiotics and sustained alleviation of renal function and brucellosis was achieved during the course of a 3-month follow-up. CONCLUSIONS Here we describe the diagnostic and treatment challenge in a patient with chronic brucellosis related glomerulonephritis accompanied by the coexistence of AAV and cryoglobulinemia. Renal biopsy confirmed the diagnosis of postinfectious acute glomerulonephritis overlapping with ANCA related crescentic glomerulonephritis, which was not ever reported in the literature. The patient showed a good response to steroid treatment which indicated the immunity-induced kidney injury. Meanwhile, it is essential to recognize and actively treat the coexisting brucellosis even when there are no clinical signs of the active stage of infection. This is the critical point for a salutary patient outcome for brucellosis associated renal complications.
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Affiliation(s)
- Xu Yang
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China
| | - Congcong Jiao
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China
| | - Xiaomei Liu
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China
| | - Yongzhe Zhang
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China
| | - Hua Zhou
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China
| | - Yanqiu Wang
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China.
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Kim SH, Erikson A, Woodfield D, DeMott C. A Rare Case of Abiotrophia Endocarditis-Associated Glomerulonephritis Mimicking ANCA Vasculitis. J Gen Intern Med 2023; 38:806-809. [PMID: 36460879 PMCID: PMC9971404 DOI: 10.1007/s11606-022-07960-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 11/15/2022] [Indexed: 12/04/2022]
Affiliation(s)
- Seo Hyun Kim
- Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
| | - Alexander Erikson
- Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
| | - David Woodfield
- Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
| | - Chad DeMott
- Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
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Chavez Y, Garces J, Díaz R, Escobar M, Sanchez A, Buendía E, Múnera M. Molecular mimicry among human proteinase 3 and bacterial antigens: implications for development of c-ANCA associated vasculitis. OXFORD OPEN IMMUNOLOGY 2022; 3:iqac009. [PMID: 36846563 PMCID: PMC9914470 DOI: 10.1093/oxfimm/iqac009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 11/08/2022] [Accepted: 11/09/2022] [Indexed: 12/03/2022] Open
Abstract
Wegener's granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through in silico analysis. Thirteen serine proteases from human pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella sp., Streptococcus suis, Vibrio parahaemolyticus, Bacteroides fragilis, Enterobacter ludwigii, Vibrio alginolyticus, Staphylococcus haemolyticus, Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59-74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90-98, 101-108, 162-169, 267 and 262 residues positions). In conclusion, this is the first report providing in silico evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener's granulomatosis.
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Affiliation(s)
- Y Chavez
- Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5–70, Cartagena 130002, Colombia
| | - J Garces
- Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5–70, Cartagena 130002, Colombia
| | - R Díaz
- Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5–70, Cartagena 130002, Colombia
| | - M Escobar
- Catholic University of Manizales, Manizales, Av. Santander #No. 60, Manizales, Caldas 111321, Colombia
| | - A Sanchez
- Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5–70, Cartagena 130002, Colombia,Group of Clinical and Experimental Allergy (GACE), IPS Universitaria, University of Antioquia, Cl 77 y 78 al norte, Antioquia, Medellín 050010, Colombia
| | - E Buendía
- Faculty of Medicine, University of Cartagena, Cra. 50 #24120, Zaragocilla, Cartagena de Indias, Provincia de Cartagena, Bolívar, Cartagena 130014, Colombia,Clinical and Biomedical Research Group, Faculty of Medicine, University of Cartagena, Cra. 50 #24120, Zaragocilla, Cartagena de Indias, Provincia de Cartagena, Bolívar, Cartagena 130014, Colombia,Serena del Mar Hospital Center, VIA AL MAR KM 8, Cartagena de Indias, Provincia de Cartagena, Bolívar, Cartagena 130008, Colombia
| | - M Múnera
- Correspondence address. Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5-70, Cartagena, Colombia. Tel: +57-300-529-5164. E-mail:
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Ai S, Liu J, Ma G, Ye W, Hu R, Zhang S, Fan X, Liu B, Miao Q, Qin Y, Li X. Endocarditis-associated rapidly progressive glomerulonephritis mimicking vasculitis: a diagnostic and treatment challenge. Ann Med 2022; 54:754-763. [PMID: 35243934 PMCID: PMC8903796 DOI: 10.1080/07853890.2022.2046288] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Infective endocarditis (IE)-associated rapidly progressive glomerulonephritis (RPGN) is rarely reported. Sporadic case reports have noted the diagnostic and therapeutic challenge in IE-associated glomerulonephritis because it may masquerade as idiopathic vasculitis. METHODS Patients with clinical diagnosis of IE-related RPGN in a tertiary hospital in China between January 2004 and May 2021 were identified and retrospectively reviewed. RESULTS Twenty-four patients with IE-associated RPGN were identified. All patients presented with fever and multiorgan system involvement on top of heart and kidneys, spleen (79%, 19/24), skin (63%, 15/24), lung (33%, 8/24) and nervous system (17%, 4/24). Six of the 24 patients (25%) were initially suspected to have ANCA-associated or IgA vasculitis. Forty-five percent of patients are seropositive for ANCA. Renal histology showed mesangial and/or endocapillary hypercellularity with extensive crescents in most patients. C3-dominant deposition was the predominant pattern on immunofluorescence and pauci-immune necrotising crescentic glomerulonephritis was observed in one case. All patients received antibiotics with or without surgery. Six patients received immunosuppressive therapy before antibiotics due to misdiagnosis and seven patients received immunosuppressive therapy after antibiotics due to persistence of renal failure. Three of the 24 patients died due to severe infection. All the surviving patients had partial or complete recovery of renal function. CONCLUSION IE-associated RPGN is rare and the differential diagnosis from idiopathic vasculitis can be challenging due to overlaps in clinical manifestations, ANCA positivity and absence of typical presentations of IE. The prognosis is generally good if antibiotics and surgery are not delayed. The decision on introducing immunoruppressive treatment should be made carefully on a case by case basis when kidney function does not improve appropriately after proper anti-infective therapy.Key messagesInfective endocarditis associated RPGN is rare and differentiating it from idiopathic vasculitis can be challenging due to overlap in clinical manifestations, ANCA positivity and occasional absence of typical manifestations of infective endocarditis.Kidney function usually responds to antibiotic therapy alone.Immunosuppressive therapy may be beneficial in carefully selected patients whose kidney function does not improve with antibiotics alone.
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Affiliation(s)
- Sanxi Ai
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jianzhou Liu
- Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Guotao Ma
- Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wenling Ye
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Rongrong Hu
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shangzhu Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaohong Fan
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bingyan Liu
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Qi Miao
- Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yan Qin
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xuemei Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Ai S, Liu X, Chen G, Zhang Y, Bai X, Qin Y, Miao Q, Li X. Characteristics and Diagnostic Challenge of Antineutrophil Cytoplasmic Antibody Positive Infective Endocarditis. Am J Med 2022; 135:1371-1377. [PMID: 35820459 DOI: 10.1016/j.amjmed.2022.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 06/17/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Antineutrophil cytoplasmic antibody (ANCA) has been reported in patients with infective endocarditis. Whether ANCA is associated with certain characteristics of infective endocarditis is unclear. The principal aim of this study is to investigate the clinical implications of ANCA in infective endocarditis and highlight the diagnostic challenge in ANCA-positive patients with infective endocarditis. METHODS A retrospective study was conducted in a tertiary hospital in China from August 2012 to December 2021. Patients with a diagnosis of infective endocarditis and available ANCA results were included in the study. The clinical and pathological characteristics were compared between ANCA-positive and ANCA-negative patients. RESULTS A total of 237 patients were included. Forty three (18.1%) were ANCA-positive, predominantly c-ANCA/anti-PR3. Compared to ANCA-negative patients, ANCA-positive patients had longer disease duration (P = .004), more frequent purpura (P = .015), macrohematuria (P = .002), proteinuria (P = .043), acute kidney injury (P = .004), and rapidly progressive glomerulonephritis (P = .010). Histologic findings of 8 patients with infective endocarditis-associated glomerulonephritis were reviewed. Two ANCA-positive patients with infective endocarditis presented with pauci-immune necrotizing and crescentic glomerulonephritis. A total of 18.6% of ANCA-positive patients with infective endocarditis were misdiagnosed as ANCA-associated vasculitis. CONCLUSIONS ANCA is detected in a substantial proportion of patients with infective endocarditis. The presence of ANCA in infective endocarditis is associated with longer disease duration, more frequent purpura, and kidney involvement. ANCA-positive infective endocarditis may mimic ANCA-associated vasculitis, and the differential diagnosis is challenging. Whether ANCA is pathogenic in infective endocarditis-associated small vessel vasculitis requires further study.
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Affiliation(s)
- SanXi Ai
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - XinPei Liu
- Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Gang Chen
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - YueLun Zhang
- Department of Medical Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xue Bai
- Department of Medical Records, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yan Qin
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Qi Miao
- Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - XueMei Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Wang F, Zhou Z, Teng J, Sun Y, You Y, Su Y, Hu Q, Liu H, Cheng X, Shi H, Yang C, Ye J. The clinical pattern differentiates ANCA-positive infective endocarditis patients from ANCA-associated vasculitis patients: a 23 years' retrospective cohort study in China and follow-ups. Clin Rheumatol 2022; 41:3439-3449. [PMID: 35906495 PMCID: PMC9562078 DOI: 10.1007/s10067-022-06313-w] [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: 03/10/2022] [Revised: 06/26/2022] [Accepted: 07/25/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Patients with infective endocarditis (IE) may present rheumatic manifestations concurrent with various autoantibodies and thus mimic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study aims to characterize the specific features in a long-term cohort of ANCA-positive IE patients and to perform comparative analysis with primary AAV patients. METHODS We performed a retrospective thorough review of 475 consecutive IE patients over 23 years, identifying 22 patients positive for proteinase 3 and/or myeloperoxidase and 36 treatment-naïve AAV patients. The clinical, laboratory, and follow-up data were collected to perform comparative analysis. RESULTS Our study illustrated that ANCA-positive IE patients were younger and had a shorter duration than AAV patients. Pulmonary lesions, ENT signs, peripheral neuropath, and proteinuria were more commonly seen in AAV patients, while heart valve involvement, spleen enlargement, and cerebral hemorrhage were more typical for IE patients (all p < 0.05). Besides, ANCA-positive IE patients presented a higher level of PR3-ANCA but lower C3 (both p < 0.05). Hyperleukocytosis and thrombocytopenia were more frequently found in AAV patients (both p < 0.05). No significant difference was noticed in the survival rate. CONCLUSIONS Our study urges the early differential diagnosis of IE in ANCA-positive patients. It supports the claim that ANCA-positive IE patients and AAV patients do not share the same clinical spectrum. Echocardiography, serological profiles, and evaluation of multi-organ involvement might be required to improve diagnostic accuracy. Key Points •Early differential diagnosis of ANCA-positive IE from AAV is challenging even for expert rheumatologists. •Our study is so far one of the largest to include 22 ANCA-positive IE patients in one single center and spanning over 23 years. It is also the first study to include both ANCA-positive IE patients and AAV patients in one center. •Our study aides to identify a clinical picture to differentiate ANCA-Positive IE Patients from AAV Patients.
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Affiliation(s)
- Fan Wang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Zhuochao Zhou
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Jialin Teng
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Yue Sun
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Yijun You
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Yutong Su
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Qiongyi Hu
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Honglei Liu
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Xiaobing Cheng
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Hui Shi
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China
| | - Chengde Yang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China.
| | - Junna Ye
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China.
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14
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Van Gool IC, Kers J, Bakker JA, Rotmans JI, Teng YKO, Bauer MP. Antineutrophil cytoplasmic antibodies in infective endocarditis: a case report and systematic review of the literature. Clin Rheumatol 2022; 41:2949-2960. [PMID: 35732985 PMCID: PMC9485185 DOI: 10.1007/s10067-022-06240-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 11/03/2022]
Abstract
Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA positivity in IE patients. We present a case report and systematic review of the literature on patients with ANCA-positive IE, aiming to provide a comprehensive overview of this entity and to aid clinicians in their decisions when encountering a similar case. A systematic review of papers on original cases of ANCA-positive IE without a previous diagnosis of AAV was conducted on PubMed in accordance with PRISMA-IPD guidelines. A predefined set of clinical, laboratory, and kidney biopsy findings was extracted for each patient and presented as a narrative and quantitative synthesis. A total of 74 reports describing 181 patients with ANCA-positive IE were included (a total of 182 cases including our own case). ANCA positivity was found in 18-43% of patients with IE. Patients usually presented with subacute IE (73%) and had positive cytoplasmic ANCA-staining or anti-proteinase-3 antibodies (79%). Kidney function was impaired in 72%; kidney biopsy findings were suggestive of immune complexes in 59%, while showing pauci-immune glomerulonephritis in 37%. All were treated with antibiotics; 39% of patients also received immunosuppressants. During follow-up, 69% of patients became ANCA-negative and no diagnosis of systemic vasculitis was reported. This study reviewed the largest series of patients with ANCA-positive IE thus far and shows the overlap in clinical manifestations between IE and AAV. We therefore emphasize that clinicians should be alert to the possibility of an underlying infection when treating a patient with suspected AAV, even when reassured by ANCA positivity. Key Points • This systematic review describes - to our knowledge - the largest series of patients with ANCA-positive infective endocarditis (IE) thus far (N=182), and shows a high degree of overlap in clinical manifestations between IE and ANCA-associated vasculitis (AAV). • ANCA positivity was found in 18-43% of patients with infective endocarditis. Of patients with ANCA-positive IE, the majority (79%) showed cytoplasmic ANCA-staining or anti-PR3-antibodies. We emphasize that clinicians should be alert to the possibility of an underlying infection when treating a patient with suspected AAV, even when reassured by ANCA positivity. • In patients with IE and ANCA-associated symptoms such as acute kidney injury, an important clinical challenge is the initiation of immunosuppressive therapy. All patients with data in this series received antibiotics; 39% also received immunosuppressive therapy. In many of these patients, ANCA-associated symptoms resolved or stabilized after infection was treated. ANCA titers became negative in 69% , and a diagnosis of AAV was made in none of the cases. We therefore recommend that (empiric) antibiotic treatment remains the therapeutic cornerstone for ANCA-positive IE patients, while a watchful wait-and-see approach with respect to immunosuppression is advised.
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Affiliation(s)
- Inge C Van Gool
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
| | - Jesper Kers
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Jaap A Bakker
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Laboratory for Genetic Metabolic Diseases, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Joris I Rotmans
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Y K Onno Teng
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Martijn P Bauer
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Pavlovich SS, Bennett WC, Terinte-Balcan G, Hladik G, Jain K. Infective Endocarditis-Associated Pauci-Immune Glomerulonephritis in a Patient With Cryoglobulinemia. Cureus 2022; 14:e27560. [PMID: 36059292 PMCID: PMC9428425 DOI: 10.7759/cureus.27560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/30/2022] [Indexed: 11/17/2022] Open
Abstract
Small-vessel vasculitis has a broad differential with similar clinical presentation and laboratory abnormalities, including petechial rashes, neurologic symptoms, glomerulonephritis, and abnormal inflammatory markers. Biopsy-based diagnosis is critical as the treatment varies by etiology. We report a case of a 41-year-old man with diagnosed cryoglobulinemia and hepatitis C presenting with a petechial rash, altered mental status, and acute kidney injury and ultimately found to have proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis secondary to infective endocarditis. Skin biopsy was consistent with resolving, but nonspecific vasculitis and MRI showed foci of hemosiderin deposition concerning vasculitic lesions. Blood cultures grew Enterococcus faecalis, and he was treated with IV antibiotics. Kidney biopsy showed pauci-immune necrotizing focal segmental glomerulonephritis (GN) and diffuse acute tubular necrosis (ATN). After blood cultures cleared, he was initially treated with mycophenolate for worsening renal function. When the patient stopped antibiotics unexpectedly, his kidney function worsened and improved only after immunosuppression was stopped and antibiotics were restarted. This case highlights the importance of renal biopsy in patients with multiple potential etiologies of GN. The case resolution also reinforces that patients with infective endocarditis causing ANCA-associated GN should be treated with antibiotics in addition to, and possibly instead of, immunosuppression.
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16
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Takata T, Mae Y, Sugihara T, Isomoto H. Infective Endocarditis-Associated Glomerulonephritis: A Comprehensive Review of the Clinical Presentation, Histopathology, and Management. Yonago Acta Med 2022; 65:1-7. [DOI: 10.33160/yam.2022.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/28/2021] [Indexed: 11/05/2022]
Affiliation(s)
- Tomoaki Takata
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Yukari Mae
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Takaaki Sugihara
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
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17
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Zhang W, Zhang H, Wu D, Fu H, Shi W, Xue F. Antineutrophil cytoplasmic antibody-positive infective endocarditis complicated by acute kidney injury: a case report and literature review. J Int Med Res 2020; 48:300060520963990. [PMID: 33078666 PMCID: PMC7583404 DOI: 10.1177/0300060520963990] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 09/10/2020] [Indexed: 11/29/2022] Open
Abstract
Patients with infective endocarditis (IE) may present with multisystem disturbances resembling autoimmune diseases, such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The kidneys are susceptible to damage in IE and AAV, which is a source of diagnostic ambiguity. Therefore, distinguishing infection from an inflammatory process is pivotal for guiding appropriate therapy. We report a 22-year-old man with IE characterized by ANCA positivity and complicated by acute kidney injury. A renal biopsy showed crescentic nephritis with tubulointerstitial lesions. However, transthoracic echocardiography and blood culture provided evidence of IE, and AAV was ruled out. Surgical intervention and antibiotic treatments were successful. We summarized previously reported cases of ANCA-positive IE that had renal biopsy data. We found that ANCA-positive IE can involve multiple organs. The representative renal pathology was crescentic nephritis, focal segmental glomerulonephritis, mesangial cell proliferation, tubular injury, and interstitial oedema. Immunofluorescence showed predominate C3 deposits. Electron microscopy showed electron-dense deposits in the subendothelial or mesangial areas. Eight patients received immunosuppressive therapy with excellent results. Repeated testing for bacterial pathogens and multiple renal biopsies may be useful for diagnosing ANCA-positive IE. With ANCA-positive IE, immunosuppressive therapy along with antibiotic treatments may be beneficial for recovery of renal function.
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Affiliation(s)
- Wei Zhang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Hui Zhang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Daoxu Wu
- Department of Nephrology, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong, China
| | - Haiyang Fu
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Weiping Shi
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Feng Xue
- Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
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Kakoullis L, Parperis K, Papachristodoulou E, Panos G. Infection-induced myeloperoxidase specific antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis: A systematic review. Clin Immunol 2020; 220:108595. [PMID: 32961330 DOI: 10.1016/j.clim.2020.108595] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS PubMed/Medline databases were searched from inception to July of 2020, according to PRISMA guidelines. RESULTS Among the 618 abstracts identified, 18 articles describing 23 patients (60.9% female, mean age 50.5 years) were included. Median time between infection and vasculitis development was 3 months. Five (21.7%) patients expired during follow-up. Vasculitis regressed after the resolution of infection in 12/23 (52.2%). ANCA titers decreased significantly on follow-up in 14/16 patients and in all survivors in which they were measured. Pathogens reported included Mycobacterium spp., Coccidioides spp., Rickettsia rickettsii, Staphylococcus spp., EBV, CMV and Dengue virus. CONCLUSIONS MPO-AAV can occur after infection and may regress after its resolution. Infection should be considered in cases of MPO-AAV, as immunosuppressive treatment can have catastrophic results if the infection is not adequately treated.
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Affiliation(s)
- Loukas Kakoullis
- Department of Respiratory Medicine, University of Patras General Hospital, Patras, Greece; Department of Internal Medicine, University of Cyprus Medical School, Nicosia, Cyprus
| | - Konstantinos Parperis
- Department of Medicine, Division of Rheumatology, University of Arizona College of Medicine, Phoenix, AZ, USA; Department of Internal Medicine, Division of Rheumatology, University of Cyprus Medical School, Nicosia, Cyprus
| | - Eleni Papachristodoulou
- Department of Internal Medicine, Division of Rheumatology, University of Cyprus Medical School, Nicosia, Cyprus
| | - George Panos
- Department of Internal Medicine, University of Cyprus Medical School, Nicosia, Cyprus; Department of Internal Medicine, Section of Infectious Diseases, University of Patras General Hospital, Patras, Greece.
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19
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Shi XD, Li WY, Shao X, Qu LM, Jiang ZY. Infective endocarditis mimicking ANCA-associated vasculitis: does it require immunosuppressive therapy?: A case report and literature review. Medicine (Baltimore) 2020; 99:e21358. [PMID: 32702934 PMCID: PMC7373528 DOI: 10.1097/md.0000000000021358] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
RATIONALE In the course of endocarditis, the development of antineutrophil cytoplasmic antibody (ANCA)-mediated disease introduces the dilemma of determining the best treatment approach for immune conditions, whether immunosuppressant therapy should be added to antibiotic treatment has remained controversial. PATIENT CONCERNS A 33-year-old man presented with progressive fever lasting for 7 months, and swelling, pain, and purpura in the arms and legs. The patient showed multiple autoantibodies including cytoplasmic ANCA, antiproteinase 3, rheumatoid factor, and anti-beta 2 glycoprotein I. Blood culture was positive for viridans streptococcus, and renal biopsy revealed glomerulonephritis and interstitial nephritis. DIAGNOSIS Endocarditis caused by viridans streptococci, ANCA-associated vasculitis, and congenital ventricular septal defect. INTERVENTIONS In addition to effective antibiotics, he also received twice intravenous corticosteroids and intravenous immunoglobulin therapy, and a low dose of cyclophosphamide. At last, the patient received congenital ventricular septal defect repair and debridement. OUTCOMES The abnormal clinical manifestations, including renal failure and loss of strength, recovered rapidly with corticosteroid therapy in addition to antibiotic treatment. After 6 months without any medications, he remained asymptomatic and was able to live normally. LESSONS In this case with endocarditis and ANCA-associated vasculitis, we highlighted the importance of biopsy and immunosuppressive therapy. Histopathologic examination is required for diagnosis and treatment in such case. Identifying patients who have endocarditis and ANCA positivity with vasculitis pathologic features will require corticosteroid/immunosuppressives in addition to the antibiotics therapy.
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Affiliation(s)
| | - Wan-yu Li
- Hepatology, First Hospital of Jilin University
| | - Xue Shao
- Hepatopancreatobiliary Medicine, Second Hospital of Jilin University
| | - Li-mei Qu
- Pathology Department, First Hospital of Jilin University, Changchun, China
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20
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Zhang Q, Shi B, Zeng H. Antineutrophil cytoplasmic antibodies (ANCA)-positive patient with infective endocarditis and chronic hepatitis B virus: a case report and review of the literature. J Med Case Rep 2020; 14:90. [PMID: 32624005 PMCID: PMC7336675 DOI: 10.1186/s13256-020-02373-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Accepted: 03/17/2020] [Indexed: 01/05/2023] Open
Abstract
Background Antineutrophil cytoplasmic antibodies comprise a family of autoantibodies that are often used as biomarkers for certain forms of small-vessel vasculitis; however, chronic infections tend to induce the production of antineutrophil cytoplasmic antibodies. Infective endocarditis and hepatitis B virus infection have been reported to exhibit antineutrophil cytoplasmic antibody positivity and to mimic antineutrophil cytoplasmic antibody–associated vasculitis, which may lead to misdiagnosis and inappropriate treatment. Case presentation We report a case of a 46-year-old Han Chinese man with untreated chronic hepatitis B virus infection who featured proteinase-3 antineutrophil cytoplasmic antibody positivity while hospitalized with infective endocarditis. Cardiac ultrasound echocardiography disclosed mitral and aortic regurgitation with vegetation. On the 15th hospital day, the patient underwent mitral and aortic valve replacement and was then treated with antibiotics for more than 1 month. On the 57th hospital day, the patient was discharged. His urinary abnormalities and renal function were gradually recovering. Four months after being discharged, his proteinase-3 antineutrophil cytoplasmic antibody levels had returned to the normal range. Conclusions The findings in this study update and expand current understanding of antineutrophil cytoplasmic antibody positivity in patients with both infective endocarditis and hepatitis B virus. Treatment (including surgery, antibiotics, corticosteroids and/or cyclophosphamide, antiviral agents, and even plasma exchange) is challenging when several diseases are combined. Renal biopsy is suggested if the patient’s condition allows. Antineutrophil cytoplasmic antibody testing should be repeated after therapy, because some cases might require more aggressive treatment.
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Affiliation(s)
- Qian Zhang
- Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Baoxian Shi
- Department of Chemistry and Environmental Engineering, Wuhan Polytechnic University, Wuhan, Hubei, People's Republic of China
| | - Hongbing Zeng
- Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
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21
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Jeffs LS, Peh CA, Nelson A, Tan PG, Davey E, Chappell K, Perkins GB, Hurtado PR. IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis. Immunol Res 2020; 67:325-336. [PMID: 31372816 DOI: 10.1007/s12026-019-09091-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Low levels of IgM auto-antibodies have been reported in health and disease. IgM anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in patients with ANCA-associated vasculitis (AAV). We sought to investigate if healthy individuals may have IgM ANCA in their sera. The first aim of the study was to determine whether IgM ANCA was present in healthy individuals and in patients with ANCA-associated vasculitis. The second aim was to determine what happens to IgM ANCA levels over time. The third aim was to determine whether bacterial infections affected IgM ANCA levels in non-AAV patients. Sera from healthy individuals and patients with AAV were tested for IgM ANCA by immunofluorescence on fixed neutrophils, immunoprecipitation, Western blot and ELISA. Peripheral blood mononuclear cells were isolated and tested by ELISpot for circulating IgM ANCA B cells. To determine whether infection affected IgM ANCA levels, we studied non-AAV patients with bacterial endocarditis or Staphylococcus aureus bacteraemia and measured IgM ANCA levels over time. IgM ANCA is detectable in both healthy individuals and patients with AAV and the titres decreased with increasing age. Circulating IgM ANCA B cells were identified by ELISpot. In the presence of infection, we could not find a significant change in IgM ANCA levels. We report the presence of low-level specific IgM ANCA in the sera of healthy individuals and in patients with ANCA-associated vasculitis. Bacterial infection did not affect the level of IgM ANCA in this small study.
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Affiliation(s)
- L S Jeffs
- Department of Nephrology, Royal Hobart Hospital, Liverpool Street, Hobart, Tasmania, 7000, Australia.
| | - C A Peh
- Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, Australia.,Faculty of Medical and Health Sciences, University of Adelaide, Adelaide, Australia
| | - A Nelson
- Faculty of Medical and Health Sciences, University of Adelaide, Adelaide, Australia.,Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia
| | - P G Tan
- Department of Nephrology, Royal Hobart Hospital, Liverpool Street, Hobart, Tasmania, 7000, Australia
| | - E Davey
- Department of Nephrology, Royal Hobart Hospital, Liverpool Street, Hobart, Tasmania, 7000, Australia
| | - K Chappell
- Menzies Institute for Medical Research, Department of Statistics, University of Tasmania, Liverpool Street, Hobart, Tasmania, 7000, Australia
| | - G B Perkins
- Faculty of Medical and Health Sciences, University of Adelaide, Adelaide, Australia
| | - P R Hurtado
- Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, Australia.,Faculty of Medical and Health Sciences, University of Adelaide, Adelaide, Australia
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22
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Hashimoto S, Aizawa T, Watanabe S, Tsugawa K, Tanaka H. Osteomyelitis-related glomerulonephritis with myeloperoxidase-antineutrophil cytoplasmic antibody positivity. Pediatr Int 2020; 62:236-238. [PMID: 32067324 DOI: 10.1111/ped.14080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/21/2019] [Accepted: 11/01/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Shun Hashimoto
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
| | - Tomomi Aizawa
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
| | - Shojiro Watanabe
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
| | - Koji Tsugawa
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
| | - Hiroshi Tanaka
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
- Department of School Health Science, Hirosaki University Faculty of Education, Hirosaki, Japan
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Bele D, Kojc N, Perše M, Černe Čerček A, Lindič J, Aleš Rigler A, Večerić-Haler Ž. Diagnostic and treatment challenge of unrecognized subacute bacterial endocarditis associated with ANCA-PR3 positive immunocomplex glomerulonephritis: a case report and literature review. BMC Nephrol 2020; 21:40. [PMID: 32005179 PMCID: PMC6995228 DOI: 10.1186/s12882-020-1694-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 01/20/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Diagnosis and treatment of either ANCA disease or silent infection-related glomerulonephritis is complicated and is a huge treatment challenge when overlapping clinical manifestations occur. We report a case of ANCA-PR3 glomerulonephritis, nervous system involvement, hepatosplenomegaly and clinically silent subacute infectious endocarditis. CASE PRESENTATION A 57-year-old man with known mitral valve prolaps was admitted for unexplained renal failure with signs of nephritic syndrome, hepatosplenomegaly, sudden unilateral hearing loss, vertigo, malaise, new onset hemolytic anemia and thrombocytopenia. Immunoserology revealed positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3), mixed type crioglobulinemia and lowered complement fraction C3. Head MRI showed many microscopic hemorrhages. Common site of infection, as well as solid malignoma were ruled out. In accordance with clinical and laboratory findings, systemic vasculitis was assumed, although the etiology remained uncertain (ANCA-associated, cryoglobulinemic or related to unrecognized infection). After kidney biopsy, clinical signs of sepsis appeared. Blood cultures revealed Streptococcus cristatus. Echocardiography showed mitral valve endocarditis. Kidney biopsy revealed proliferative, necrotizing immunocomplex glomerulonephritis. Half a year later, following intravenous immunoglobulins, glucocorticoids, antibiotic therapy and surgical valve repair, the creatinine level decreased and c-ANCA and cryoglobulins disappeared. A second kidney biopsy revealed no residual kidney disease. Four years after treatment, the patient is stable with no symptoms or signs of vasculitis recurrence. CONCLUSIONS Here we describe the diagnostic and treatment challenge in a patient with unrecognized subacute bacterial endocarditis associated with ANCA-PR3 immunocomplex proliferative and crescentic glomerulonephritis. In patients with ANCA-PR3 immunocomplex glomerulonephritis and other overlapping manifestations suggesting systemic disease, it is important to recognize and aggressively treat any possible coexisting bacterial endocarditis, This is the most important step for a favorable patient outcome, including complete clinical and pathohistological resolution of the glomerulonephritis.
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Affiliation(s)
- D. Bele
- Department of Cardiology, General Hospital Novo mesto, Novo mesto, Slovenia
| | - N. Kojc
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - M. Perše
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Medical Experimental Center, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - A. Černe Čerček
- Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - J. Lindič
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - A. Aleš Rigler
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Ž. Večerić-Haler
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
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Leaver PJ, Jang HS, Wong MG, Soh HC, Fernando SL. ANCA-associated vasculitis of the appendix. Rheumatol Adv Pract 2019; 3:rkz037. [PMID: 31650102 PMCID: PMC6800888 DOI: 10.1093/rap/rkz037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 09/14/2019] [Indexed: 11/12/2022] Open
Affiliation(s)
| | | | - Muh G Wong
- Department of Renal Medicine, Royal North Shore Hospital.,Department of Medicine, The University of Sydney
| | - Hwei-Choo Soh
- Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Suran L Fernando
- Department of Clinical Immunology and Allergy.,Department of Medicine, The University of Sydney
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25
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Alba MA, Jennette JC, Falk RJ. Pathogenesis of ANCA-Associated Pulmonary Vasculitis. Semin Respir Crit Care Med 2018; 39:413-424. [PMID: 30404109 DOI: 10.1055/s-0038-1673386] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Antineutrophil cytoplasmic antibodies (ANCAs) are autoantibodies specific for antigens located in the cytoplasmic granules of neutrophils and lysosomes of monocytes. ANCAs are associated with a spectrum of necrotizing vasculitis that includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Pulmonary vasculitis and related extravascular inflammation and fibrosis are frequent components of ANCA vasculitis. In this review, we detail the factors that have been associated with the origin of the ANCA autoimmune response and summarize the most relevant clinical observations, in vitro evidence, and animal studies strongly indicating the pathogenic potential of ANCA. In addition, we describe the putative sequence of pathogenic mechanisms driven by ANCA-induced activation of neutrophils that result in small vessel necrotizing vasculitis and extravascular granulomatous necrotizing inflammation.
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Affiliation(s)
- Marco A Alba
- Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - J Charles Jennette
- Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Ronald J Falk
- University of North Carolina Kidney Center, Chapel Hill, North Carolina.,UNC Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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26
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Hanna RM, So N, Kaldas M, Hou J, Arman F, Sangalang M, Yanny B, Selamet U, Saab S, Nobakht N, Rastogi A. Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis. Case Rep Nephrol Dial 2018; 8:161-170. [PMID: 30197905 PMCID: PMC6120379 DOI: 10.1159/000491629] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/28/2018] [Indexed: 01/21/2023] Open
Abstract
Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.
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Affiliation(s)
- Ramy M Hanna
- UCLA-Southbay Nephrology, Rancho Palos Verdes, California, USA.,UCLA David Geffen School of Medicine, Westwood, California, USA
| | - Naomi So
- UCLA David Geffen School of Medicine, Westwood, California, USA
| | - Marian Kaldas
- UCLA David Geffen School of Medicine, Westwood, California, USA.,UCLA Health-Southbay Rheumatology, Torrance, California, USA
| | - Jean Hou
- Cedars Sinai Medical Center, Renal Pathology, Los Angeles, California, USA
| | - Farid Arman
- UCLA David Geffen School of Medicine, Westwood, California, USA
| | - Michelle Sangalang
- UCLA David Geffen School of Medicine, Westwood, California, USA.,UCLA Southbay Family Medicine, Rancho Palos Verdes, California, USA
| | - Bishoy Yanny
- UCLA-Southbay Nephrology, Rancho Palos Verdes, California, USA.,UCLA David Geffen School of Medicine, Westwood, California, USA
| | - Umut Selamet
- UCLA-Southbay Nephrology, Rancho Palos Verdes, California, USA.,UCLA David Geffen School of Medicine, Westwood, California, USA
| | - Sammy Saab
- UCLA David Geffen School of Medicine, Westwood, California, USA.,UCLA Ronald Regan Medical Center, Department of Medicine, Division of Hepatology, Westwood, California, USA
| | | | - Anjay Rastogi
- UCLA David Geffen School of Medicine, Westwood, California, USA
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27
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Abstract
Systemic vasculitides frequently affect the pulmonary vasculature. As the signs and symptoms of pulmonary vasculitis are variable and nonspecific, diagnosis and treatment represent a real challenge. Vasculitides should be given consideration, as these diseases present severe manifestations of rapidly progressing pulmonary disease. Examining other organs usually affected by vasculitides (e.g., the skin and kidneys) and determining autoantibody levels are essential to a better management of the disease. A radiological study would also contribute to establishing a diagnosis. The lungs are commonly involved in small-vessel vasculitis, anti-glomerular basement membrane disease, and vasculitides associated with antineutrophil cytoplasmic antibodies. Associated life-threatening diffuse alveolar haemorrhages and irreversible damage to other organs-usually the kidneys-are severe complications that require early diagnosis. Vasculitides are rare diseases that affect multiple organs. An increasing number of treatments-including biological agent-based therapies-requiring cooperation between specialists and centers have become available in the recent years. In the same way, clinicians should be familiar with the complications associated with immunosuppressive therapies.
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Affiliation(s)
| | | | | | | | | | - Luis Valdés
- Interdisciplinary Research Group in Pneumology, Institute of Sanitary Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
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28
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Yang L, Xie H, Liu Z, Chen Y, Wang J, Zhang H, Ge Y, Hu W. Risk factors for infectious complications of ANCA-associated vasculitis: a cohort study. BMC Nephrol 2018; 19:138. [PMID: 29902982 PMCID: PMC6002994 DOI: 10.1186/s12882-018-0933-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 05/25/2018] [Indexed: 12/05/2022] Open
Abstract
Background Severe infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement. We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy. Methods A total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study. The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Results A total of 103 episodes of severe infection were identified in 86 (34.7%, 86/248) patients during a median follow-up of 15 months. The incidence of infection during induction therapy was 38.5% for corticosteroids (CS), 39.0% for CS+ intravenous cyclophosphamide (IV-CYC), 33.8% for CS+ mycophenolate mofetil and 22.5% for CS + tripterygium glycosides, 76 (73.8%) infection episodes occurred within 6 months, while 66 (64.1%) occurred within 3 months. Pneumonia (71.8%, 74/103) was the most frequent type of infection, and the main pathogenic spectrum included bacteria (78.6%), fungi (12.6%), and viruses (8.7%). The risk factors associated with infection were age at the time of diagnosis (HR = 1.003, 95% CI = 1.000–1.006), smoking (HR = 2.338, 95% CI = 1.236–4.424), baseline secrum creatinine (SCr) ≥5.74 mg/dl (HR = 2.153, 95% CI = 1.323–3.502), CD4+ T cell< 281 μl (HR = 1.813, 95% CI = 1.133–2.900), and intravenous cyclophosphamide regimen (HR = 1.951, 95% CI =1.520–2.740). Twelve (13.9%) patients died of severe pneumonia. Conclusion The infection rate during induction therapy was high in patients with AAV. Bacterial pneumonia was the main type of infection encountered. Age at the time of diagnosis, smoking, baseline SCr ≥5.74 mg/dl, CD4+ T cell< 281 μl, and IV-CYC therapy were identified as risk factors for infection.
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Affiliation(s)
- Liu Yang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Honglang Xie
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Zhengzhao Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Yinghua Chen
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Jinquan Wang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Haitao Zhang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Yongchun Ge
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
| | - Weixin Hu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
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Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement. Pediatr Nephrol 2018; 33:1-11. [PMID: 27596099 DOI: 10.1007/s00467-016-3475-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Revised: 05/18/2016] [Accepted: 05/25/2016] [Indexed: 01/20/2023]
Abstract
The antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitides (AAV), although rare in childhood, can have devastating effects on affected organs, especially the kidney. In this review we present an update on the pathogenesis and treatment of ANCA vasculitis, with a particular emphasis on the role of the alternative pathway of complement. The rationale and evidence for the current treatment strategies are summarized. Targeting the activation of neutrophils by the anaphylatoxin C5a may serve as an additional therapeutic strategy, however the results of clinical studies are awaited.
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30
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Langlois V, Marie I. Endocardites infectieuses associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) : revue de la littérature. Rev Med Interne 2017; 38:450-457. [DOI: 10.1016/j.revmed.2016.12.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 12/15/2016] [Accepted: 12/26/2016] [Indexed: 12/19/2022]
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Sato N, Yokoi H, Imamaki H, Uchino E, Sakai K, Matsubara T, Tsukamoto T, Minamiguchi S, Yanagita M. Renal-limited vasculitis with elevated levels of multiple antibodies. CEN Case Rep 2017; 6:79-84. [PMID: 28509135 DOI: 10.1007/s13730-017-0248-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 01/18/2017] [Indexed: 10/20/2022] Open
Abstract
Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis with no other organ involvement. Although several studies reported patients with crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive patients, were rarely reported. We herein report the case of a male with pauci-immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and anti-GBM antibody. Renal biopsy led to the definitive diagnosis of RLV with pauci-immune-type crescentic glomerulonephritis. Fluorescence immunostaining showed no linear deposition of IgG on GBM, indicating no involvement of anti-GBM associated diseases. Intensive therapy, including prednisolone, plasma exchange, and intravenous cyclophosphamide, was effective. We report the case of triple-positive patient with crescentic glomerulonephritis, who was successfully treated with glucocorticoid, plasma exchange, and cyclophosphamide, suggesting that treatment for RLV in the patient with serological triple antibodies positivity in the absence of linear IgG deposition could benefit from the combination therapy regimen for plasma exchange and primary induction of remission against microscopic polyangiitis.
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Affiliation(s)
- Noriaki Sato
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan
| | - Hideki Yokoi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.
| | - Hirotaka Imamaki
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.,Department of Nephrology, Hirakata Kohsai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hirakata, Japan
| | - Eiichiro Uchino
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan
| | - Kaoru Sakai
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan
| | - Takeshi Matsubara
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan
| | - Tatsuo Tsukamoto
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.,Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan
| | | | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan
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32
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Androsova TV, Kozlovskaya LV, Taranova MV, Strizhakov LA, Gulyaev SV, Russkikh AV. Difficulties in the differential diagnosis of kidney injury in a patient with infective endocarditis associated with antineutrophil cytoplasmic antibodies. TERAPEVT ARKH 2017; 89:84-88. [DOI: 10.17116/terarkh201789684-88] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Induction of proteinase 3-anti-neutrophil cytoplasmic autoantibodies by proteinase 3-homologous bacterial protease in mice. Immunol Res 2016; 64:438-44. [PMID: 26318749 DOI: 10.1007/s12026-015-8687-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Proteinase 3 (PR3) is the principal target of antineutrophil cytoplasmic autoantibodies (ANCA) associated with granulomatosis with polyangiitis. The aim of this study was to investigate whether bacterial PR3-homologous protease can induce autoantibodies to PR3 and ANCA-associated pathology in mice. Among the bacterial proteases that have greater than 30 % identity with PR3, a trypsin-like serine protease of Saccharomonospora viridis, a bacterium that causes hypersensitivity pneumonitis, was chosen. When the mice were immunized with the recombinant protease of S. viridis (SvPR), 75 % of NZBWF1 and 100 % of C57BL/6 mice developed high levels of autoantibodies to mouse PR3 (mPR3). The levels of antibodies to mPR3 had a strong positive correlation with those to SvPR. In addition, more than half of the mPR3-reactive sera (63 %) reacted to purified human PR3 (hPR3), and the levels of antibodies to hPR3 had a positive correlation with those to mPR3. The sera from the immunized mice strongly stained murine neutrophils in a C-ANCA pattern. Although granulomatous inflammation and signs of vasculitis were observed in several mice, they were attributable to the use of complete Freund's adjuvant in the immunization. Collectively, exposure to PR3-homologous bacterial protease could induce ANCA in mice, and this finding may provide a new insight into the triggering mechanisms for the production of PR3-ANCA.
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Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male. Clin Rheumatol 2016; 35:2369-72. [DOI: 10.1007/s10067-016-3337-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Revised: 05/13/2016] [Accepted: 06/19/2016] [Indexed: 10/21/2022]
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Karlon WJ, Naides SJ, Crosson JT, Ansari MQ. Variability in Testing for Antineutrophil Cytoplasmic Antibodies: A Survey of Participants in the College of American Pathologists Proficiency Testing Program. Arch Pathol Lab Med 2016; 140:524-8. [PMID: 27232346 DOI: 10.5858/arpa.2015-0221-cp] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT -Variability in testing for antineutrophil cytoplasmic antibodies (ANCAs) contributes to confusion and controversy related to testing for vasculitis and other ANCA-associated diseases. OBJECTIVES -To survey laboratory testing practices regarding ANCA testing and to investigate differences in testing algorithms. DESIGN -Supplemental questions were sent to the 333 laboratories participating in the College of American Pathologists proficiency testing program for ANCA as part of the Special Immunology S2 Survey. RESULTS -A total of 315 laboratories submitted responses to the supplemental questions. Only 88 of 315 participants (28%) reported using a combination of indirect immunofluorescence (IFA) and enzyme immunoassay (EIA) techniques as recommended by current guidelines, with a few additional labs using IFA and multiplex bead assay as an acceptable alternative to EIA. Other labs reported using only IFA, EIA, or multiplex bead assays. CONCLUSIONS -A wide variety of testing algorithms are in use for ANCA testing despite evidence to suggest that a combination of IFA and EIA testing provides the most comprehensive information. Laboratories should inform clinicians clearly about testing practices and utility of testing in specific disease states.
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Affiliation(s)
- William J Karlon
- From the Department of Laboratory Medicine, University of California, San Francisco (Dr Karlon); Quest Diagnostics Nichols Institute, San Juan Capistrano, California (Dr Naides); the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (Dr Crosson); and the Department of Clinical Pathology, Cleveland Clinic, Cleveland, Ohio (Dr Ansari)
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Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2016; 2016:3585860. [PMID: 27366166 PMCID: PMC4904576 DOI: 10.1155/2016/3585860] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 12/21/2015] [Indexed: 11/17/2022]
Abstract
While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections.
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Langlois V, Lesourd A, Girszyn N, Ménard JF, Levesque H, Caron F, Marie I. Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis. Medicine (Baltimore) 2016; 95:e2564. [PMID: 26817911 PMCID: PMC4998285 DOI: 10.1097/md.0000000000002564] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 12/17/2015] [Accepted: 12/28/2015] [Indexed: 12/23/2022] Open
Abstract
To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA.Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed.Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients.Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients' outcome.
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Affiliation(s)
- Vincent Langlois
- From the Department of Internal Medicine, Institute for Biochemical Research, IFRMP, University of Rouen (VL, AL, NG, HL, IM); Department of Infectious diseases (FC); and Department of Biostatistics (J-F M), CHU Rouen, France
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Kronbichler A, Gut N, Zwerina J, Neuwirt H, Rudnicki M, Mayer G. Extending the spectrum of a chameleon: IgG4-related disease appearing as interstitial nephritis and mimicking anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatology (Oxford) 2015; 54:1936-8. [PMID: 26163289 DOI: 10.1093/rheumatology/kev248] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
| | - Nadezda Gut
- Department of Pathology, Medical University of Innsbruck, Innsbruck and
| | - Jochen Zwerina
- Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria
| | - Hannes Neuwirt
- Department of Internal Medicine IV (Nephrology and Hypertension)
| | - Michael Rudnicki
- Department of Internal Medicine IV (Nephrology and Hypertension)
| | - Gert Mayer
- Department of Internal Medicine IV (Nephrology and Hypertension)
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Rowaiye OO, Kusztal M, Klinger M. The kidneys and ANCA-associated vasculitis: from pathogenesis to diagnosis. Clin Kidney J 2015; 8:343-50. [PMID: 26034600 PMCID: PMC4440467 DOI: 10.1093/ckj/sfv020] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2014] [Accepted: 03/05/2015] [Indexed: 12/20/2022] Open
Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of pauci-immune small vessel vasculitides that often affect the kidneys manifesting as rapidly progressive glomerulonephritis. Although the exact pathogenesis of AAV is not fully known, evidence from in vitro, in vivo and clinical studies all point to the involvement of ANCA in the pathogenesis of AAV. In this review, we highlight the contributory roles played by various factors (e.g. genetics, environment, B and T-regulatory cells, toll-like receptors, etc.) in the pathogenesis of AAV. Furthermore, we discuss renal involvement in AAV in terms of clinical features and the various histopathological classification patterns, which are also known to be of prognostic importance. We also present information on useful imaging techniques for localizing kidney and other organ system involvement in AAV, and also on novel laboratory methods and assays useful for rapid and more specific determination of patients' ANCA status. Finally, we demonstrate evidence on novel serum biomarkers that have been shown to correlate with disease activity in AAV.
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Affiliation(s)
| | - Mariusz Kusztal
- Department of Nephrology and Transplantation Medicine , Wroclaw Medical University , Wroclaw , Poland
| | - Marian Klinger
- Department of Nephrology and Transplantation Medicine , Wroclaw Medical University , Wroclaw , Poland
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Lin MW, Silvestrini RA, Culican S, Campbell D, Fulcher DA. A dual-fixed neutrophil substrate improves interpretation of antineutrophil cytoplasmic antibodies by indirect immunofluorescence. Am J Clin Pathol 2014; 142:325-30. [PMID: 25125622 DOI: 10.1309/ajcpg02fgqvausiu] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
OBJECTIVES To determine whether the addition of a formalin-fixed neutrophil substrate could improve interpretation and prediction of autoantigenic specificity in antineutrophil cytoplasmic antibody (ANCA) testing. METHODS Routine diagnostic samples sent for ANCA testing were analyzed prospectively on a dual substrate of both ethanol- and formalin-fixed neutrophils. Positive samples on ethanol-fixed neutrophils were deemed "typical" if formalin-fixed neutrophils also stained, and "atypical" if not. Indirect immunofluorescence (IIF) results were correlated with antimyeloperoxidase (MPO) and anti-proteinase 3 (PR3) results with an enzyme-linked immunosorbent assay (ELISA). RESULTS Of 1,426 samples, 201 from unique patients were ANCA-positive (200 on IIF, 1 on ELISA alone). Thirty-two (45%) of 71 typical ANCA staining patterns were positive for either an anti-MPO or anti-PR3 antibodies, whereas only one (0.8%) of 129 atypical patterns was ELISA-positive, in a patient without systemic vasculitis. Only one (3%) of 34 ELISA-positive samples had a negative IIF-ANCA (1/1,426 patients, 0.07%), and this patient did not have vasculitis. CONCLUSIONS Concomitant staining on formalin fixation of IIF-positive ethanol-fixed ANCA samples improves the interpretation of ANCA testing and is predictive of vasculitis autoantigens MPO and PR3.
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Affiliation(s)
- Ming-Wei Lin
- Department of Immunopathology, Pathology West, ICPMR, Westmead Hospital, Westmead, Australia
- Discipline of Medicine, Sydney Medical School, University of Sydney, Sydney, Australia
| | - Roger A. Silvestrini
- Department of Immunopathology, Pathology West, ICPMR, Westmead Hospital, Westmead, Australia
| | - Suzanne Culican
- Department of Immunopathology, Pathology West, ICPMR, Westmead Hospital, Westmead, Australia
| | - David Campbell
- Department of Immunopathology, Pathology West, ICPMR, Westmead Hospital, Westmead, Australia
| | - David A. Fulcher
- Department of Immunopathology, Pathology West, ICPMR, Westmead Hospital, Westmead, Australia
- Discipline of Medicine, Sydney Medical School, University of Sydney, Sydney, Australia
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Antineutrophil cytoplasmic antibody frequency in chronic hepatitis B patients. DISEASE MARKERS 2014; 2014:982150. [PMID: 25161336 PMCID: PMC4138952 DOI: 10.1155/2014/982150] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 07/07/2014] [Accepted: 07/08/2014] [Indexed: 01/10/2023]
Abstract
Background. Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients. Methods. A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays. Results. ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P = 0.6 and P = 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P = 0.009 and P = 0.005, resp.). Conclusions. In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions.
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Gao JJ, Wei JM, Gao YH, Li S, Na Y. Central venous catheter infection-induced Henoch-Schönlein purpura in a patient on hemodialysis. Ren Fail 2014; 36:1145-7. [PMID: 24845224 DOI: 10.3109/0886022x.2014.917765] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A 69-year-old man, who had been dialyzed using a permanent central venous catheter for 2 years, presented with Henoch-Schönlein purpura and positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). He was diagnosed with catheter-related infection by Staphylococcus aureus. After administration of antibiotic and steroid therapy, purpura disappeared and p-ANCA gradually became negative. This case supports the conclusion that infection can be pathogenesis of the vasculitis, including ANCA-positive HSP. Additionally, impregnation of catheters with antibiotics can be an effective treatment for catheter infections.
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Affiliation(s)
- Jian Jun Gao
- Department of Nephrology, the 306th Hospital of Chinese PLA , Beijing , China
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43
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Lima I, Oliveira RC, Cabral MS, Atta A, Marchi S, Reis E, Reis MG, Barbosa L, Santiago MB. Anti-PR3 and anti-MPO antibodies are not present in sera of patients with pulmonary tuberculosis. Rheumatol Int 2014; 34:1231-4. [DOI: 10.1007/s00296-014-3009-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 03/28/2014] [Indexed: 10/25/2022]
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Yang DH, Ho LJ, Lai JH. Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders. World J Gastroenterol 2014; 20:2962-2970. [PMID: 24659887 PMCID: PMC3961981 DOI: 10.3748/wjg.v20.i11.2962] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/10/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.
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Infective endocarditis with antineutrophil cytoplasmic antibody: report of 13 cases and literature review. PLoS One 2014; 9:e89777. [PMID: 24587028 PMCID: PMC3934949 DOI: 10.1371/journal.pone.0089777] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 01/24/2014] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE Chronic infections tend to induce the production of antineutrophil cytoplasmic antibody (ANCA). Infective endocarditis (IE) has been reported to exhibit positive ANCA tests and to mimic ANCA-associated vasculitis, which may lead to a misdiagnosis and inappropriate treatment. The aim of this study was to clarify whether there is any difference in the clinical features between ANCA-positive IE and ANCA-negative IE. METHODS A retrospective study was carried out on 39 IE patients whose proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA levels were measured. After dividing the patients into ANCA-positive and ANCA-negative IE, we compared their clinical features. RESULTS we compared 13 ANCA-positive IE patients with 26 ANCA-negative IE patients. All 13 ANCA-positive IE patients were proteinase-3-ANCA positive. Compared with the ANCA-negative IE group, the prevalence of edema of the lower extremities, the serum lactate dehydrogenase (LDH) level and positive blood cultures rate were higher in ANCA-positive IE group, but there was no significant difference in other clinical features. CONCLUSION Therefore, if a patient presents with fever, arthralgia, skin rash and is ANCA-positive, appropriate steps should be taken to exclude infection (especially IE) before confirming the diagnosis of ANCA-associated vasculitis and embarking on long-term immunosuppressive therapy.
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Papp M, Sipeki N, Vitalis Z, Tornai T, Altorjay I, Tornai I, Udvardy M, Fechner K, Jacobsen S, Teegen B, Sumegi A, Veres G, Lakatos PL, Kappelmayer J, Antal-Szalmas P. High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis. J Hepatol 2013; 59:457-466. [PMID: 23639483 DOI: 10.1016/j.jhep.2013.04.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2012] [Revised: 04/12/2013] [Accepted: 04/16/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. METHODS Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. RESULTS Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p<0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p<0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p<0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18-2.56, p=0.006). CONCLUSIONS Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents.
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Affiliation(s)
- Maria Papp
- 2nd Department of Medicine, Division of Gastroenterology, University of Debrecen, Debrecen, Hungary.
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Rousseau-Gagnon M, Riopel J, Desjardins A, Garceau D, Agharazii M, Desmeules S. Gemella sanguinis endocarditis with c-ANCA/anti-PR-3-associated immune complex necrotizing glomerulonephritis with a 'full-house' pattern on immunofluorescence microscopy. Clin Kidney J 2013; 6:300-4. [PMID: 26064489 PMCID: PMC4400477 DOI: 10.1093/ckj/sft030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 02/26/2013] [Indexed: 01/23/2023] Open
Abstract
A 67-year-old man was evaluated for haematuria, with a rising creatinine level from 88 to 906 µmol/L and positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3). A kidney biopsy revealed necrotizing glomerulonephritis with a ‘full-house’ pattern on immunofluorescence microscopy. Echocardiography and blood cultures growing Gemella sanguinis diagnosed endocarditis. Dialysis was required for a month. Three months later, following valve replacement, glucocorticoids and 2 months of antibiotic therapy, the creatinine level decreased to 62 µmol/L and c-ANCA/anti-PR3 disappeared. This first case of c-ANCA/anti-PR3 positive glomerulonephritis with a ‘full-house’ immunofluorescence pattern due to bacterial endocarditis underlines the importance of ruling out infection with ANCA positivity or kidney biopsy suggestive of lupus nephritis.
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Affiliation(s)
| | - Julie Riopel
- Service of Pathology , CHUQ-Hôtel-Dieu de Québec , Quebec , Canada
| | - Anne Desjardins
- Service of Infectious Diseases , CHUQ-Hôtel-Dieu de Québec , Quebec , Canada
| | | | - Mohsen Agharazii
- Service of Nephrology , CHUQ-Hôtel-Dieu de Québec , Quebec , Canada
| | - Simon Desmeules
- Service of Nephrology , CHUQ-Hôtel-Dieu de Québec , Quebec , Canada
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Veerappan I, Prabitha EN, Abraham A, Theodore S, Abraham G. Double ANCA-positive vasculitis in a patient with infective endocarditis. Indian J Nephrol 2013; 22:469-72. [PMID: 23439873 PMCID: PMC3573492 DOI: 10.4103/0971-4065.106057] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The most common pattern of renal involvement in infective endocarditis is infection-associated glomerulonephritis. Due to clinical symptoms and signs that overlap with vasculitis, the diagnosis of infective endocarditis may be delayed. The unusual combination of reduced complement with positive antineutrophil cytoplasmic antibody should raise the suspicion of infections such as infective endocarditis.
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Affiliation(s)
- I Veerappan
- Department of Nephrology, Pondicherry Institute of Medical Sciences, Puducherry, India
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Konstantinov KN, Emil SN, Barry M, Kellie S, Tzamaloukas AH. Glomerular disease in patients with infectious processes developing antineutrophil cytoplasmic antibodies. ISRN NEPHROLOGY 2013; 2013:324315. [PMID: 24959541 PMCID: PMC4045435 DOI: 10.5402/2013/324315] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 11/06/2012] [Indexed: 12/21/2022]
Abstract
To identify differences in treatment and outcome of various types of glomerulonephritis developing in the course of infections triggering antineutrophil cytoplasmic antibody (ANCA) formation, we analyzed published reports of 50 patients. Immunosuppressives were added to antibiotics in 22 of 23 patients with pauci-immune glomerulonephritis. Improvement was noted in 85% of 20 patients with information on outcomes. Death rate was 13%. Corticosteroids were added to antibiotics in about 50% of 19 patients with postinfectious glomerulonephritis. Improvement rate was 74%, and death rate was 26%. Two patients with mixed histological features were analyzed under both pauci-immune and post-infectious glomerulonephritis categories. In 9 patients with other renal histology, treatment consisted of antibiotics alone (7 patients), antibiotics plus immunosuppressives (1 patient), or immunosuppressives alone (1 patient). Improvement rate was 67%, permanent renal failure rate was 22%, and death rate was 11%. One patient with antiglomerular basement disease glomerulonephritis required maintenance hemodialysis. Glomerulonephritis developing in patients who became ANCA-positive during the course of an infection is associated with significant mortality. The histological type of the glomerulonephritis guides the choice of treatment. Pauci-immune glomerulonephritis is usually treated with addition of immunosuppressives to antibiotics.
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Affiliation(s)
- Konstantin N. Konstantinov
- Division of Rheumatology, Department of Medicine, Raymond G. Murphy VA Medical Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
| | - Suzanne N. Emil
- Division of Rheumatology, Department of Medicine, Raymond G. Murphy VA Medical Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
| | - Marc Barry
- Department of Pathology, University of New Mexico School of Medicine, MSC08 4640, BMSB, Room 335, University of New Mexico, Albuquerque, NM 87131, USA
| | - Susan Kellie
- Division of Infectious Diseases, Department of Medicine, Raymond G. Murphy VA Medical Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
| | - Antonios H. Tzamaloukas
- Division of Nephrology, Department of Medicine, Raymond G. Murphy VA Medical Center, University of New Mexico School of Medicine, VA Medical Center (111C), 1501 San Pedro, SE, Albuquerque, NM 87131, USA
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Peng H, Chen WF, Wu C, Chen YR, Peng B, Paudel SD, Lou TQ. Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with polyangiitis (Wegener's granulomatosis) involving both the kidney and lung. BMC Nephrol 2012; 13:174. [PMID: 23268737 PMCID: PMC3574827 DOI: 10.1186/1471-2369-13-174] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2012] [Accepted: 12/19/2012] [Indexed: 11/23/2022] Open
Abstract
Background Subacute bacterial endocarditis (SBE) occasionally exhibits positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) of the anti-proteinase-3 (PR-3) type. Clinically, it mimics ANCA-associated vasculitis, such as Wegener's disease with glomerulonephritis. Lung abscesses are the most common manifestation of lung involvement. We herein report a case of culture-negative SBE strongly c-ANCA/PR3-positive accompanied by pulmonary involvement and glomerulonephritis. In this case, we took biopsies of both the lung and kidney, although renal biopsy is usually preferred over lung biopsy. The lung biopsy showed severe alveolar capillaritis, suggesting vasculitis consistent with polyangiitis. The renal biopsy revealed glomerulonephritis with a membranoproliferative pattern. To our knowledge, this is the first such reported case. Case presentation A 68-year-old Chinese male patient presented to our hospital with a fever, cough, chest pain, and recurrent peripheral edema. He had a past medical history significant for treated schistosomiasis 20 years previously. Physical examination revealed palpable purpura, mild hypertension, hepatosplenomegaly, and a holosystolic cardiac murmur (Levine 2/6). Echocardiography showed tricuspid valve vegetations with moderate to severe regurgitation. Serum c-ANCA/PR3 and cryoglobulin were strongly positive. Renal biopsy results indicated membranoproliferative glomerulonephritis with several crescents. Chest CT revealed multiple intraparenchymal and subpleural nodules, and lung biopsy showed polyangiitis. The patient’s ANCA titers, glomerulonephritis, and pulmonary injury all resolved after antibiotic therapy. Conclusion SBE may present with positive c-ANCA/PR3, multiple pulmonary nodules, pulmonary polyangiitis, and glomerulonephritis clinically mimicking granulomatosis with polyangiitis (Wegener's granulomatosis).
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Affiliation(s)
- Hui Peng
- Division of Nephrology, Department of Medicine, The third affiliated hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China.
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