|
1
|
Avasare RS, Andeen NK, Al-Rabadi LF, Burfeind KG, Beck LH. Drug-Induced Membranous Nephropathy: Piecing Together Clues to Understand Disease Mechanisms. J Am Soc Nephrol 2025:00001751-990000000-00608. [PMID: 40198910 DOI: 10.1681/asn.0000000719] [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: 11/30/2024] [Accepted: 03/28/2025] [Indexed: 04/10/2025] Open
Abstract
There is a resurgence of interest in drug-induced membranous nephropathy because of the widespread availability of recently discovered culprit medications, such as lipoic acid supplements, mercury in skin-lightening creams, and nonsteroidal anti-inflammatory drugs, and the relationship between these drugs and newly described target antigens. The clinical syndromes associated with drug-induced membranous nephropathy are similar in that proteinuria ranges from low grade to nephrotic range and generally remits within months of drug cessation. Histology is notable for subepithelial deposits that are IgG1 subclass predominant, sometimes with a unique segmental distribution. The two antigens associated with drug-induced membranous nephropathy are neural epidermal growth factor-like 1 and proprotein convertase subtilisin/kexin type 6. Notably, several of the culprit drugs contain one or more sulfhydryl groups that may have potential mechanistic relevance. In this review, we explore past research investigations into mechanisms of membranous nephropathy associated with gold salts, penicillamine, and mercury and use these historical studies as the basis for formulating new hypotheses on how drugs might promote immune dysregulation and, ultimately, membranous nephropathy.
Collapse
Affiliation(s)
- Rupali S Avasare
- Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, Oregon
| | - Nicole K Andeen
- Department of Pathology, Oregon Health and Science University, Portland, Oregon
| | - Laith F Al-Rabadi
- Division of Nephrology, Department of Medicine, University of Utah, Salt Lake City, Utah
| | - Kevin G Burfeind
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon
| | - Laurence H Beck
- Section of Nephrology, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts
| |
Collapse
|
|
2
|
Mohamed Siraj H, Ali M, Sharma SS, Begum A, Ahmad MH, Hassan M, Aref Elsayed RKMK, Tahir MH. Drug-Induced Renal Vasculitis: Etiology, Pathogenesis, Clinical Manifestations, and Therapeutic Approaches-A Narrative Review. Health Sci Rep 2025; 8:e70667. [PMID: 40242254 PMCID: PMC12001824 DOI: 10.1002/hsr2.70667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 02/21/2025] [Accepted: 03/21/2025] [Indexed: 04/18/2025] Open
Abstract
Background and Aims Drug-induced renal vasculitis arises from various medications that cause immunological dysregulation or direct vascular damage, leading to inflammation and thrombosis. Clinical manifestations vary widely, from mild constitutional symptoms to severe organ dysfunction. This review aims to thoroughly explore drug-induced renal vasculitis, focusing on its etiology, pathological mechanisms, clinical manifestations, diagnostic challenges, and therapeutic approaches. This review aims to summarize current knowledge and highlight areas requiring further research. Methods A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library databases. We included peer-reviewed journal articles and excluded those with insufficient data, poor quality, or lack of relevance. The search terms included combinations of "renal vasculitis," "drug-induced vasculitis," "drug-related nephritis," "medication-induced renal vasculitis," and specific drug names. An initial search yielded 13,192 articles, of which 13,103 were excluded due to irrelevance, duplication, or outdated information. After full-text review, 99 peer-reviewed articles were included. Results Discontinuation of the offending drug is the primary and most crucial step in managing drug-induced renal vasculitis. Prognosis is generally more favorable than primary vasculitis, with a high remission rate if the offending drug is stopped early. Due to its rarity, epidemiological data is limited. Diagnosis frequently relies on autoantibodies [antineutrophil cytoplasm antibodies (ANCA), myeloperoxidase (MPO), antinuclear antibody (ANA)] and clinical symptoms, with renal biopsy confirming it. Factors such as high-dose and long-term drug use, as well as genetic predispositions, increase the risk. Conclusion This review provides a comprehensive overview of drug-induced renal vasculitis, discussing what is known and identifying gaps in understanding. While discontinuing the causative drug remains the cornerstone of management, further research is needed, particularly in developing a formal tool to assess the quality of studies and minimize selection bias.
Collapse
Affiliation(s)
| | - Masab Ali
- Department of Internal MedicinePunjab Medical CollegeFaisalabadPunjabPakistan
| | | | - Afreen Begum
- Department of MedicineESIC Medical College and HospitalHyderabadTelanganaIndia
| | - Muhammad Husnain Ahmad
- Department of MedicineTentishev Satkynbai Memorial Asian Medical InstituteKantKyrgyzstan
| | - Muhammad Hassan
- Department of Internal MedicinePunjab Medical CollegeFaisalabadPunjabPakistan
| | | | | |
Collapse
|
|
3
|
Sharma P, Zonozi R, Geetha D. ANCA-Associated Vasculitis. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:194-205. [PMID: 39004459 DOI: 10.1053/j.akdh.2024.04.005] [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: 08/02/2023] [Revised: 04/19/2024] [Accepted: 04/24/2024] [Indexed: 07/16/2024]
Abstract
ANCA-associated vasculitis (AAV) is a necrotizing, small-to-medium vessel vasculitis associated with significant morbidity and mortality. AAV is a systemic autoimmune disease affecting kidneys, eyes, sinuses, peripheral nerves, skin, and upper and lower respiratory tracts. AAV tends to present in characteristic phenotypes categorized clinically as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). Kidney involvement is a common feature of AAV, and has important implications on disease prognosis and management. Existing therapies have been refined and improvements in our understanding of the pathophysiology of AAV has led to approval of novel therapies. In this review, we provide an overview of epidemiology, disease mechanisms, clinical presentation and review therapeutic strategies for induction and maintenance of remission.
Collapse
Affiliation(s)
- Purva Sharma
- Division of Kidney Disease and Hypertension, Northwell Health, The Glomerular Disease Center at Northwell Health.
| | - Reza Zonozi
- Nephrology Associates of Northern Virginia, Fairfax, VA; Inova Fairfax Hospital, Falls Church, VA
| | - Duvuru Geetha
- Division of Nephrology, Johns Hopkins University School of Medicine
| |
Collapse
|
|
4
|
Panda K, Lal BB, Sood V, Khanna R, Alam S. Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease. J Pediatr Gastroenterol Nutr 2024; 78:1017-1026. [PMID: 38695602 DOI: 10.1002/jpn3.12128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 12/11/2023] [Accepted: 12/24/2023] [Indexed: 06/16/2024]
Abstract
OBJECTIVES Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.
Collapse
Affiliation(s)
- Kalpana Panda
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant B Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| |
Collapse
|
|
5
|
Panda K, Lal BB, Sood V, Khanna R, Alam S. Relapse following withdrawal of D‐penicillamine from combination (D‐penicillamine + zinc) therapy in hepatic Wilson disease. J Pediatr Gastroenterol Nutr 2024; 78:1017-1026. [DOI: https:/doi.org/10.1002/jpn3.12128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
AbstractObjectivesLong‐term D‐penicillamine (D‐pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D‐pen from combination (D‐pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD.MethodsHepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24‐h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin‐bound‐copper (NCC) <15 mcg/dL. After D‐pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier.ResultsForty‐five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D‐pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox‐regression, ALT at D‐pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014–1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity.ConclusionIncidence of relapse after withdrawal of D‐pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D‐pen stoppage, predicts future relapse.
Collapse
Affiliation(s)
- Kalpana Panda
- Department of Pediatric Hepatology Institute of Liver and Biliary Sciences New Delhi India
| | - Bikrant B. Lal
- Department of Pediatric Hepatology Institute of Liver and Biliary Sciences New Delhi India
| | - Vikrant Sood
- Department of Pediatric Hepatology Institute of Liver and Biliary Sciences New Delhi India
| | - Rajeev Khanna
- Department of Pediatric Hepatology Institute of Liver and Biliary Sciences New Delhi India
| | - Seema Alam
- Department of Pediatric Hepatology Institute of Liver and Biliary Sciences New Delhi India
| |
Collapse
|
|
6
|
Dang J, Chevalier K, Letavernier E, Tissandier C, Mouawad S, Debray D, Obadia M, Poujois A. Kidney involvement in Wilson's disease: a review of the literature. Clin Kidney J 2024; 17:sfae058. [PMID: 38660122 PMCID: PMC11040517 DOI: 10.1093/ckj/sfae058] [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: 12/05/2023] [Indexed: 04/26/2024] Open
Abstract
Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.
Collapse
Affiliation(s)
- Julien Dang
- Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, France
- Centre de Compétence Maladies Rares «Syndrome Néphrotique Idiopathique», Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Kevin Chevalier
- Hôpital Fondation Rothschild, Service de Neurologie, Paris, France
- Centre de Référence de la Maladie de Wilson et autres Maladies Rares Liées au Cuivre, Paris, France
| | - Emmanuel Letavernier
- AP-HP, Hôpital Tenon, Service des Explorations Fonctionnelles Multidisciplinaires, Paris, France
| | - Come Tissandier
- Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, France
- Centre de Compétence Maladies Rares «Syndrome Néphrotique Idiopathique», Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Sarah Mouawad
- Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, France
- Centre de Compétence Maladies Rares «Syndrome Néphrotique Idiopathique», Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Dominique Debray
- Hôpital Fondation Rothschild, Service de Neurologie, Paris, France
- Centre de Référence de la Maladie de Wilson et autres Maladies Rares Liées au Cuivre, Paris, France
| | - Mickaël Obadia
- Hôpital Fondation Rothschild, Service de Neurologie, Paris, France
- Centre de Référence de la Maladie de Wilson et autres Maladies Rares Liées au Cuivre, Paris, France
| | - Aurélia Poujois
- Hôpital Fondation Rothschild, Service de Neurologie, Paris, France
- Centre de Référence de la Maladie de Wilson et autres Maladies Rares Liées au Cuivre, Paris, France
| |
Collapse
|
|
7
|
Athanasopoulou D, Lionaki S, Skalioti C, Liapis G, Vlachoyiannopoulos P, Boletis I. Drug-Induced Podocytopathies: Report of Four Cases and Review of the Literature. Life (Basel) 2023; 13:1264. [PMID: 37374047 DOI: 10.3390/life13061264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
Kidney injury due to medications is a well-known clinical entity. Although drug-induced tubulointerstitial disease is commonly encountered, there are few reports in the literature associated with glomerular injury due to medications. The recognition of this type of kidney injury is crucial, as rapid discontinuation of the offending agent is critical to maximizing the likelihood of quick and effective renal function recovery. In this article, we present four cases that presented with nephrotic syndrome and were diagnosed with biopsy-proven podocytopathies, associated with exposure to a certain medication. All of them experienced complete resolution of nephrotic syndrome within days or weeks after discontinuation of the offending drug. We also present the data, which were found in a Medline search from the year 1963 until the present, regarding cases with podocytopathies associated with penicillamine, tamoxifen and the combination of pembrolizumab-axitinib, including only adult cases from the English literature. The Medline search revealed nineteen cases of penicillamine-induced minimal-change disease (MCD), one case of tamoxifen-induced MCD, and none associated with pembrolizumab-axitinib therapy. We also searched for the largest studies and meta-analyses regarding drug-induced podocytopathies after a Medline search from 1967 to the present of the English literature.
Collapse
Affiliation(s)
- Diamanto Athanasopoulou
- Department of Nephrology and Transplantation, National and Kapodistrian University of Athens, Laiko Hospital, 115 27 Athens, Greece
| | - Sophia Lionaki
- Department of Nephrology, National and Kapodistrian University of Athens, Attiko Hospital, 124 62 Athens, Greece
| | - Chrysanthi Skalioti
- Department of Nephrology and Transplantation, National and Kapodistrian University of Athens, Laiko Hospital, 115 27 Athens, Greece
| | - George Liapis
- Department of Pathology, National and Kapodistrian University of Athens, Laiko Hospital, 115 27 Athens, Greece
| | - Panayiotis Vlachoyiannopoulos
- Department of Pathophysiology, National and Kapodistrian University of Athens, Laiko Hospital, 115 27 Athens, Greece
| | - Ioannis Boletis
- Department of Nephrology and Transplantation, National and Kapodistrian University of Athens, Laiko Hospital, 115 27 Athens, Greece
| |
Collapse
|
|
8
|
Folci M, Ramponi G, Solitano V, Brunetta E. Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis. Clin Rev Allergy Immunol 2022; 63:107-123. [PMID: 34460071 DOI: 10.1007/s12016-021-08887-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2021] [Indexed: 01/13/2023]
Abstract
Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.
Collapse
Affiliation(s)
- Marco Folci
- Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.
| | | | - Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Enrico Brunetta
- Humanitas Clinical and Research Center - IRCCS, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| |
Collapse
|
|
9
|
Abstract
PURPOSE OF REVIEW Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. RECENT FINDINGS The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, and subspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.
Collapse
|
|
10
|
Antczak‐Kowalska M, Członkowska A, Eyileten C, Palejko A, Cudna A, Wolska M, Piechal A, Litwin T. Autoantibodies in Wilson disease: Impact on clinical course. JIMD Rep 2022; 63:508-517. [PMID: 36101827 PMCID: PMC9458613 DOI: 10.1002/jmd2.12317] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 07/02/2022] [Accepted: 07/11/2022] [Indexed: 11/21/2022] Open
Abstract
Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D-penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.
Collapse
Affiliation(s)
| | - Anna Członkowska
- 2nd Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
| | - Ceren Eyileten
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical PharmacologyMedical University of WarsawWarsawPoland
| | - Anna Palejko
- 2nd Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
| | - Agnieszka Cudna
- 2nd Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical PharmacologyMedical University of WarsawWarsawPoland
| | - Marta Wolska
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical PharmacologyMedical University of WarsawWarsawPoland
- Doctoral School, Medical University of WarsawWarsawPoland
| | - Agnieszka Piechal
- 2nd Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical PharmacologyMedical University of WarsawWarsawPoland
| | - Tomasz Litwin
- 2nd Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
| |
Collapse
|
|
11
|
Seetharaman J, Sarma MS. Chelation therapy in liver diseases of childhood: Current status and response. World J Hepatol 2021; 13:1552-1567. [PMID: 34904029 PMCID: PMC8637676 DOI: 10.4254/wjh.v13.i11.1552] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/07/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson’s disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.
Collapse
Affiliation(s)
- Jayendra Seetharaman
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| |
Collapse
|
|
12
|
D-penicillamine in Wilson's disease; recognizing the transition from benefit to harm. eNeurologicalSci 2021; 23:100328. [PMID: 33786384 PMCID: PMC7994719 DOI: 10.1016/j.ensci.2021.100328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/12/2021] [Accepted: 02/02/2021] [Indexed: 11/22/2022] Open
|
|
13
|
Cao XY, Liu H, Xu D, Li MT, Wang Q, Jiang L, Hou Y, Zhu LX, Zeng XF. Patterns of renal pathology in Chinese patients with systemic sclerosis undergoing renal biopsy at a tertiary medical center. J Int Med Res 2020; 48:300060519894456. [PMID: 31878823 PMCID: PMC7783277 DOI: 10.1177/0300060519894456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 11/21/2019] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE We investigated renal injury characteristics in Chinese patients with systemic sclerosis (SSc) who had undergone renal biopsy. METHODS We searched the medical records of patients with SSc who were hospitalized at Peking Union Medical College Hospital between January 1990 and August 2019. We analyzed the clinical characteristics and pathological results of these patients. RESULTS We identified 25 patients who had undergone renal biopsy. Of these patients, 10 had scleroderma renal crisis (SRC); one underwent renal biopsy twice (for diffuse mesangial proliferative glomerulonephritis and for SRC); two had antineutrophil cytoplasmic antibody-associated glomerulonephritis; one had immunoglobulin M nephropathy; one had minimal change nephropathy; seven had lupus nephritis; one had scleroderma renal crisis with comorbid lupus nephritis; and two had drug-related kidney injury (caused by aristolochic acid in one and D-penicillamine in the other). Acute tubular necrosis was observed in the patient taking oral aristolochic acid, while minimal change nephropathy was observed in the patient with D-penicillamine-induced renal injury. CONCLUSIONS SRC was the most commonly encountered renal damage in patients with SSc. We recommend biopsy for patients undergoing treatment for SRC who have persistent renal injury with proteinuria, regardless of hematuria. Rheumatologists in Eastern countries should be aware of aristolochic acid nephropathy.
Collapse
Affiliation(s)
- Xiao-yu Cao
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - He Liu
- Department of Ultrasound, Peking
Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking
Union Medical College, Beijing, China
| | - Dong Xu
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Meng-tao Li
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Qian Wang
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Li Jiang
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Yong Hou
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Li-xiu Zhu
- Department of Rheumatology, Ningde
Hospital Affiliated to Fujian Medical University, Ningde, Fujian Province,
China
| | - Xiao-feng Zeng
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| |
Collapse
|
|
14
|
D-penicillamine-induced autoimmune disorders. Dig Liver Dis 2019; 51:1741-1742. [PMID: 31669076 DOI: 10.1016/j.dld.2019.08.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/26/2019] [Accepted: 08/27/2019] [Indexed: 12/11/2022]
|
|
15
|
Kang S, Cho MH, Hyun H, Kim JH, Ko JS, Kang HG, Cheong HI, Kim WS, Moon KC, Ha IS. A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome. J Korean Med Sci 2019; 34:e173. [PMID: 31222986 PMCID: PMC6589402 DOI: 10.3346/jkms.2019.34.e173] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 06/03/2019] [Indexed: 12/15/2022] Open
Abstract
D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.
Collapse
Affiliation(s)
- Sena Kang
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Myung Hyun Cho
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Hyesun Hyun
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Ji Hyun Kim
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Hee Gyung Kang
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
- Kidney Institute, Seoul National University Medical Research Center, Seoul, Korea
| | - Hae Il Cheong
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
- Kidney Institute, Seoul National University Medical Research Center, Seoul, Korea
| | - Woo Sun Kim
- Department of Radiology, Seoul National University Children's Hospital, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
| | - Kyung Chul Moon
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Il Soo Ha
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
- Kidney Institute, Seoul National University Medical Research Center, Seoul, Korea.
| |
Collapse
|
|
16
|
Abstract
The availability of effective therapies distinguishes Wilson disease (WD) from other inherited neurometabolic diseases. The cause of hepatic, neurologic or psychiatric symptoms is copper overload and subsequent copper toxicity. Diagnosed WD patients require life-long pharmacologic therapy that is focused on reversal of copper overload with maintenance of a long-term negative copper balance. This is associated with the rapid control of free or non-ceruloplasmin bound copper that is mostly responsible for acute cytotoxic effects. Currently available therapies can be divided into chelators and zinc salts. They have different mechanisms of action and the onset of efficacy that influences their selection in acute and chronic stages of therapy. We review the use of D-penicillamine and trientine for chelation therapies, including the required monitoring of therapy for its efficacy and possible overtreatment with iatrogenic copper deficiency. Additionally, the use of zinc salts is also discussed, including a possibility of its use for the initial therapy in an acute stage of the disease. Supportive and symptomatic therapies for liver failure and neuropsychiatric symptoms are also reviewed.
Collapse
Affiliation(s)
- Peter Hedera
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
| |
Collapse
|
|
17
|
Luqmani RA, Águeda A, O'Neill L. Small- and Medium-Vessel Primary Vasculitis. Clin Immunol 2019. [DOI: 10.1016/b978-0-7020-6896-6.00058-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
18
|
Martín-Nares E, Zuñiga-Tamayo D, Hinojosa-Azaola A. Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity. Clin Rheumatol 2018; 38:97-106. [PMID: 30006919 DOI: 10.1007/s10067-018-4212-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 07/05/2018] [Accepted: 07/09/2018] [Indexed: 12/24/2022]
Abstract
We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.
Collapse
Affiliation(s)
- Eduardo Martín-Nares
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, CP 14000, Mexico City, Mexico
| | - Diego Zuñiga-Tamayo
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, CP 14000, Mexico City, Mexico
| | - Andrea Hinojosa-Azaola
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, CP 14000, Mexico City, Mexico.
| |
Collapse
|
|
19
|
Aggarwal A, Bhatt M. Advances in Treatment of Wilson Disease. TREMOR AND OTHER HYPERKINETIC MOVEMENTS (NEW YORK, N.Y.) 2018. [PMID: 29520330 PMCID: PMC5840318 DOI: 10.7916/d841881d] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background Wilson disease (WD) is an inherited neurometabolic disorder that results in excessive copper deposition in the liver and the brain, affecting children and young adults. Without treatment the disease is invariably fatal. Though treatments for WD have been available since the 1950s, the disease continues to be associated with considerable morbidity and mortality because of missed diagnosis, and delayed or inadequate treatment. In this paper we survey WD-related literature in order to review recent advances in WD treatment. Methods We performed a literature search using the PubMed database for articles relating to WD and its medical treatment. We reviewed the articles, and cross-references of relevant articles, to summarize the current practices for treatment of WD. Results The survey shows that if WD is properly treated, in most patients the liver can be stabilized, even severe neurological disability reversed, and patients can resume normal lives. Discussion Medical treatment for WD includes use of copper chelators (penicillamine, trientine, dimercaprol, dimercaptopropane sulfonate, and ammonium tetrathiomolybdate) and drugs that decrease gastrointestinal copper absorption. Our knowledge of the treatment approaches has benefited from the large systematic clinical studies that have been conducted over the last decade. For each drug used to treat WD, we surveyed its development, indication for use, dosing, efficacy, and adverse effects.
Collapse
Affiliation(s)
- Annu Aggarwal
- Wilson Disease Clinic, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India
| | - Mohit Bhatt
- Wilson Disease Clinic, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India
| |
Collapse
|
|
20
|
Calatroni M, Oliva E, Gianfreda D, Gregorini G, Allinovi M, Ramirez GA, Bozzolo EP, Monti S, Bracaglia C, Marucci G, Bodria M, Sinico RA, Pieruzzi F, Moroni G, Pastore S, Emmi G, Esposito P, Catanoso M, Barbano G, Bonanni A, Vaglio A. ANCA-associated vasculitis in childhood: recent advances. Ital J Pediatr 2017; 43:46. [PMID: 28476172 PMCID: PMC5420084 DOI: 10.1186/s13052-017-0364-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/02/2017] [Indexed: 02/07/2023] Open
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort.
Collapse
Affiliation(s)
- Marta Calatroni
- Dialysis and Transplantation Policlinico IRCCS Fondazione San Matteo and University of Pavia, Pavia, Italy
| | - Elena Oliva
- Nephrology Unit, University Hospital, Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Davide Gianfreda
- Nephrology Unit, University Hospital, Parma, Via Gramsci 14, 43126 Parma, Italy
| | | | - Marco Allinovi
- Pediatric Nephrology Unit, Meyer Children’s University Hospital, Florence, Italy
| | | | | | - Sara Monti
- Policlinico IRCCS Fondazione San Matteo, University of Pavia, Pavia, Italy
| | - Claudia Bracaglia
- Division of Rheumatology IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Giulia Marucci
- Division of Rheumatology IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Monica Bodria
- Nephrology, Istituto G. Gaslini, Genoa, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | | | - Gabriella Moroni
- Nephrology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Serena Pastore
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy
| | - Giacomo Emmi
- Internal Medicine, University of Firenze, Florence, Italy
| | - Pasquale Esposito
- Dialysis and Transplantation Policlinico IRCCS Fondazione San Matteo and University of Pavia, Pavia, Italy
| | | | | | | | - Augusto Vaglio
- Nephrology Unit, University Hospital, Parma, Via Gramsci 14, 43126 Parma, Italy
| |
Collapse
|
|
21
|
|
|
22
|
Agarwal A, Agrawal A, Nathan K, Roy S. Rare adverse effect of a common drug: nitrofurantoin-induced ANCA-associated vasculitis. BMJ Case Rep 2015; 2015:bcr-2014-209253. [PMID: 25935915 DOI: 10.1136/bcr-2014-209253] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Nitrofurantoin is commonly prescribed to treat urinary tract infections (UTI). Reported adverse effects include gastrointestinal, pulmonary, hepatic and neurological disorders. We report a case of a 67-year-old woman treated for UTI with nitrofurantoin who presented with antineutrophilic cytoplasmic antibody (ANCA)-associated renal and skin vasculitis 3 days after starting treatment. The symptoms resolved following withdrawal of the drug and treatment with steroids. This is the first reported case of nitrofurantoin causing ANCA-associated vasculitis.
Collapse
Affiliation(s)
| | - Abhinav Agrawal
- Department of Internal Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA
| | - Karim Nathan
- Department of Internal Medicine, Cooper University Hospital, Camden, New Jersey, USA
| | - Satyajeet Roy
- Department of Internal Medicine, Cooper University Hospital, Camden, New Jersey, USA
| |
Collapse
|
|
23
|
Manabe S, Banno M, Nakano M, Fujii T, Fujiwara M, Kita Y, Nitta K, Hatano M. Bucillamine-induced membranous nephropathy with crescent formation in a patient with rheumatoid arthritis: case report and literature review. Case Rep Nephrol Dial 2015; 5:30-8. [PMID: 25849672 PMCID: PMC4294451 DOI: 10.1159/000368826] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Bucillamine is a disease-modifying antirheumatic drug that is structurally similar to D-penicillamine. The major renal side effect of bucillamine and D-penicillamine is proteinuria caused by membranous nephropathy (MN). In addition to MN, combined crescent formation has been occasionally reported in D-penicillamine-induced MN, while crescent formation has been rarely reported in bucillamine-treated cases. Here, we describe a 76-year-old female who presented with nephrotic syndrome and rapidly progressive glomerulonephritis. She was receiving bucillamine as initial treatment for recently diagnosed rheumatoid arthritis, and renal biopsy showed MN with crescent formation. To the best of our knowledge, this is the first report of bucillamine-induced MN with crescent formation in the English literature.
Collapse
Affiliation(s)
- Shun Manabe
- Department of Nephrology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Mayuko Banno
- Department of Nephrology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Marie Nakano
- Department of Nephrology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Teruhiro Fujii
- Department of Nephrology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Michio Fujiwara
- Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Yasuhiko Kita
- Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Kosaku Nitta
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan
| | - Michiyasu Hatano
- Department of Nephrology, Yokohama Rosai Hospital, Yokohama, Japan
| |
Collapse
|
|
24
|
Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Curr Opin Rheumatol 2014; 26:42-9. [PMID: 24276086 DOI: 10.1097/bor.0000000000000014] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease resulting in small-vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 or myeloperoxidase. Legal drug culprits have been implicated as causative agents in secondary forms of disease, and a recent burst of reports also implicate levamisole-adulterated cocaine as a culprit. RECENT FINDINGS Here, we briefly discuss all drug culprits associated with ANCA vasculitis and then focus on clinical, serologic, therapeutic and mechanistic aspects of four main drug culprits receiving attention of late, namely hydralazine, minocycline, propylthiouracil (PTU) and levamisole-adulterated cocaine. SUMMARY Hydralazine, minocycline, propylthiouracil and levamisole-adulterated cocaine use should be closely considered in any patient where ANCA vasculitis is entertained given the wide use of these drugs in the community. Furthermore, medical practitioners should test urine for the presence of cocaine in any patient with presumed ANCA vasculitis, and if positive, then urine should also be tested for levamisole. Clinical features can be severe requiring not only drug cessation and supportive care, but also immunosuppression, plasma exchange in severe cases and dialysis as needed. Clinical trial investigators should strongly consider excluding patients with drug-induced forms of disease and mechanistic inroads are greatly needed in these secondary forms of disease to help elucidate the underlying cause and pathogenesis of ANCA vasculitis.
Collapse
|
|
25
|
Rapidly progressive crescentic glomerulonephritis: Early treatment is a must. Autoimmun Rev 2014; 13:723-9. [DOI: 10.1016/j.autrev.2014.02.007] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 02/14/2014] [Indexed: 12/19/2022]
|
|
26
|
Mokuda S, Onishi M, Takasugi K. D-penicillamine-induced glomerulonephritis with crescent formation: Remission following drug discontinuation. Indian J Nephrol 2013; 23:226-8. [PMID: 23814426 PMCID: PMC3692153 DOI: 10.4103/0971-4065.111862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We report a 71-year-old female who presented with rheumatoid arthritis complicated by proteinuria. She had been receiving D-penicillamine (D-Pc) for two years prior to presentation. A urinalysis showed proteinuria and hematuria which disappeared within 3 months after D-Pc was stopped. The renal histological findings showed focal proliferative glomerulonephritis with crescent formation. A total of 10 cases of D-Pc-induced glomerulonephritis with crescent formation without alveolar hemorrhage have previously been reported in the literature. To the best of our knowledge, this is the first case report in which the patient did not require any treatment.
Collapse
Affiliation(s)
- S Mokuda
- Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, Matsuyama City, Ehime, Japan
| | | | | |
Collapse
|
|
27
|
Ishak R, Abbas O. Penicillamine revisited: historic overview and review of the clinical uses and cutaneous adverse effects. Am J Clin Dermatol 2013; 14:223-33. [PMID: 23605177 DOI: 10.1007/s40257-013-0022-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.
Collapse
Affiliation(s)
- Rim Ishak
- Department of Dermatology, American University of Beirut Medical Center, Riad El Solh/Beirut, P.O. Box 11-0236, Beirut 1107 2020, Lebanon
| | | |
Collapse
|
|
28
|
Quéméneur T, Mouthon L, Cacoub P, Meyer O, Michon-Pasturel U, Vanhille P, Hatron PY, Guillevin L, Hachulla E. Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature. Medicine (Baltimore) 2013; 92:1-9. [PMID: 23263715 PMCID: PMC5370746 DOI: 10.1097/md.0b013e31827781fd] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis. We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc). Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage.
Collapse
Affiliation(s)
- Thomas Quéméneur
- From the Department of Nephrology and Internal Medicine (TQ, PV), Hospital of Valenciennes, Valenciennes; Université Paris Descartes, National Reference Centre for Scleroderma and Systemic Vasculitis (LM, LG), Cochin Hospital, Paris; Department of Internal Medicine (PC), AP-HP, Hôpital Pitié-Salpêtrière, Paris; Department of Rheumatology (OM), Bichat Hospital, Paris; Department of Vascular Medicine (UMP), Saint-Joseph Hospital, Paris; and Department of Internal Medicine, National Reference Centre for Scleroderma (PYH, EH), Claude Huriez Hospital, University of Lille, Lille, France
| | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Dong QY, Wu ZY. Advance in the pathogenesis and treatment of Wilson disease. Transl Neurodegener 2012; 1:23. [PMID: 23210912 PMCID: PMC3526418 DOI: 10.1186/2047-9158-1-23] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 11/21/2012] [Indexed: 02/06/2023] Open
Abstract
Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need.
Collapse
Affiliation(s)
- Qin-Yun Dong
- Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Zhi-Ying Wu
- Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| |
Collapse
|
|
30
|
Chen M, Gao Y, Guo XH, Zhao MH. Propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis. Nat Rev Nephrol 2012; 8:476-83. [PMID: 22664738 DOI: 10.1038/nrneph.2012.108] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of potentially life-threatening autoimmune diseases. A recent development in this field is the recognition that certain drugs can induce AAV. Among these agents, the drug most often implicated in causing disease is the commonly used antithyroid agent propylthiouracil (PTU). This Review provides an update on PTU-induced AAV. Clinical characteristics of PTU-induced AAV are similar to that of primary AAV, but usually have a milder course and better prognosis, provided early cessation of the disease-causing drug. PTU-induced ANCAs usually react to several components of myeloid granules, which is helpful in differentiating PTU-induced AAV from primary AAV. Early cessation of PTU is crucial in the treatment of PTU-induced AAV. The duration of immunosuppressive therapy might be shorter than in primary AAV, depending on the severity of organ damage, and maintenance therapy is not always necessary.
Collapse
Affiliation(s)
- Min Chen
- Renal Division, Department of Medicine, Peking University First Hospital, Xicheng District, Beijing 100034, China
| | | | | | | |
Collapse
|
|
31
|
ANCA-associated vasculitis in systemic sclerosis report of 3 cases. Rheumatol Int 2012; 33:139-43. [PMID: 22238029 DOI: 10.1007/s00296-011-2359-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2011] [Accepted: 12/22/2011] [Indexed: 02/06/2023]
Abstract
The aim of the study was to describe the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in systemic sclerosis (SSc) patients. SSc patients who developed biopsy-proven AAV were identified. Their clinical manifestations, autoantibodies, presentation with vasculitis, treatment and outcome were described and compared with previously reported patients with these two conditions. Of 985 patients, 3 were identified. All patients had interstitial lung disease, and all presented with acute renal failure, proteinuria and hematuria, and were P-ANCA- and anti-Scl-70-positive. One required hemodialysis. Two were hypertensive; additionally, one patient had sinusitis, and another had monoarthritis and a macular rash. All were treated with high-dose corticosteroids and responded to therapy and attained remission at 6 months. At 1 year, one patient died of pneumonia. ANCA-associated vasculitis is a rare but serious finding in SSc patients. Positive anti-Scl-70 antibody is found commonly in these patients. Different treatment modalities are effective. Serious infections can complicate therapy and lead to death.
Collapse
|
|
32
|
Granata A, Floccari F. Membranous glomerulonephritis with superimposed ANCA-associated vasculitis: another case report. NDT Plus 2011; 4:80-1. [PMID: 25984116 PMCID: PMC4421644 DOI: 10.1093/ndtplus/sfq198] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2010] [Revised: 10/21/2010] [Accepted: 10/26/2010] [Indexed: 11/14/2022] Open
Affiliation(s)
- Antonio Granata
- Department of Nephrology and Dialysis , "V. Emanuele" Hospital , Catania , Italy
| | - Fulvio Floccari
- Department of Nephrology and Dialysis , "San Paolo" Hospital , Civitavecchia , Italy
| |
Collapse
|
|
33
|
GAO YING, ZHAO MINGHUI. Review article: Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton) 2009; 14:33-41. [DOI: 10.1111/j.1440-1797.2009.01100.x] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
34
|
Hanukoglu A, Curiel B, Berkowitz D, Levine A, Sack J, Lorberboym M. Hypothyroidism and dyshormonogenesis induced by D-penicillamine in children with Wilson's disease and healthy infants born to a mother with Wilson's disease. J Pediatr 2008; 153:864-6. [PMID: 19014823 DOI: 10.1016/j.jpeds.2008.06.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2007] [Revised: 05/12/2008] [Accepted: 06/17/2008] [Indexed: 12/22/2022]
Abstract
Two siblings born to a mother with Wilson's disease, who was taking D-penicillamine, developed transient goitrous hypothyroidism. A prospective evaluation of 5 patients with Wilson's disease taking and not taking D-penicillamine for as long as 9.5 years showed subclinical hypothyroidism. D-penicillamine probably inhibited thyroperoxidase activity in utero in healthy infants and during childhood in patients with Wilson's disease.
Collapse
Affiliation(s)
- Aaron Hanukoglu
- Division of Pediatric Endocrinology, E. Wolfson Medical Center, Holon, Israel; Tel-Aviv University, Sackler School of Medicine, Israel
| | | | | | | | | | | |
Collapse
|
|
35
|
Abstract
Gold salts have been used in the treatment of patients with rheumatoid arthritis since 1927 [1]. After a controlled study, the Empire Rheumatism Council [2], confirmed the effectiveness of gold salts for the treatment of rheumatoid arthritis. Even today, chrysotherapy has remained one of the major therapeutic modalities in the second line treatment of progressive rheumatoid arthritis. Gold salts are also used in the treatment of pemphigus vulgaris [3] and bronchial asthma [4]. Before the introduction of an orally administered gold compound, auranofin (triethylphosphine gold tetra-acetyl glycopyranoside), to clinical use [5-7], parenterally administered gold salts, such as sodium aurothiomalate and gold thioglucose comprised chrysotherapy. The frequency and severity of the side effects for patients treated with parenteral gold versus those given oral gold preparations are significantly different [8-10]. With introduction of newer parental DMARDs, toxicity has been reduced using combination therapy [10a, 10b].
Collapse
|