|
1
|
Huang H, Zhang LL, Zhou J, Li M, Zeng X, Xu D. Bibliometric insights into systemic sclerosis with renal involvement: trends, contributions, and future directions. Ren Fail 2025; 47:2463583. [PMID: 39995144 PMCID: PMC11864008 DOI: 10.1080/0886022x.2025.2463583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/25/2025] [Accepted: 02/01/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Renal involvement is not uncommon in patients with systemic sclerosis (SSc) and presents in various forms, particularly progressing to scleroderma renal crisis (SRC), which is associated with poor prognosis. Therefore, understanding the research trends in this field is critical for advancing clinical management and therapeutic strategies. METHODS A bibliometric analysis was conducted using the Web of Science Core Collection, examining publications related to SSc and renal involvement from January 2000 to November 2024. We analyzed publication trends, key contributors, institutions, and countries. RESULTS A total of 1,339 publications were identified in the field of SSc and renal involvement, demonstrating an upward trend in publication volume from 2000 to 2024. These articles have been cited a total of 61,234 times, with the majority of contributions coming from the United States, Italy, and East Asian countries. The University of Michigan and University College London were particularly prominent in terms of both publication volume and collaboration networks. Keyword analysis revealed a shift in research focus, with increasing attention on clinical aspects, pathophysiological mechanisms, and vascular complications. CONCLUSIONS This study provides a comprehensive overview of the research landscape on SSc with renal involvement, highlighting the key contributors and emerging trends.
Collapse
Affiliation(s)
- Haochen Huang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ling-ling Zhang
- Department of Rheumatology and Clinical Immunology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Jiaxin Zhou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| |
Collapse
|
|
2
|
Laamech R, Giovannini D, Cellot E, Jost S, Franko B. Malignant hypertension, and if it was scleroderma? Lessons from two cases. Blood Press 2025; 34:2482741. [PMID: 40109088 DOI: 10.1080/08037051.2025.2482741] [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: 01/29/2025] [Revised: 03/14/2025] [Accepted: 03/14/2025] [Indexed: 03/22/2025]
Abstract
Inroduction : Scleroderma Renal Crisis (SRC) is characterised by acute hypertension, haemolytic anaemia (HA), and acute kidney injury (AKI). Often presenting as the first manifestation of scleroderma, it is frequently mistaken for malignant hypertension (MHT). Rapid recognition and differentiation of SRC from other hypertensive emergencies are essential for improving patient outcomes.We present two clinical cases that illustrate the diagnostic challenges of SRC in the context of MHT. Case 1: A 53-year-old man presented with severe hypertension (238/127 mmHg) and AKI (creatinine 390 μmol/L). He was diagnosed MHT due to the presence of grade III hypertensive retinopathy and HA. . However, a urine dipstick test detected haematuria, leading to further immune testing and, a renal biopsy, which confirmed SRC. Treatment with high-dose ramipril led to a sustained recovery of kidney function, 221 μmol/L after five years). Case 2: A 52-year-old man presented with chest pain, severe hypertension (253/132 mmHg), and AKI (creatinine 183 μmol/L). Initially managed as MHT, his kidney function worsened, prompting further investigation, which revealed haematuria and positive anti-nuclear antibodies. A renal biopsy confirmed SRC. High-dose ramipril was reintroduced, leading to partial kidney function recovery (creatinine 218 μmol/L after five years). Key findings : These cases underscore the importance of early detection of hematuria and autoimmune markers to expedite diagnosis of SRC in case of MHT. When SRC is suspected, high-dose angiotensin-converting enzyme inhibitors (ACEi) should be initiated immediately, even before biopsy confirmation and continued despite initial kidney function decline. Early intervention is crucial for optimising kidney outcomes and achieving effective blood pressure control.
Collapse
Affiliation(s)
- Réda Laamech
- Service de néphrologie et hypertension artérielle, Centre Hospitalier Annecy Genevois, Épagny Metz-Tessy, France
| | - Diane Giovannini
- Service d'Anatomie et de Cytologie Pathologiques, CHU Grenoble Alpes, Grenoble, France
| | - Etienne Cellot
- Service de néphrologie et hypertension artérielle, Centre Hospitalier Annecy Genevois, Épagny Metz-Tessy, France
| | - Sandra Jost
- Service de Cardiologie, Centre Hospitalier Annecy Genevois, Épagny Metz-Tessy, France
| | - Benoit Franko
- Service de néphrologie et hypertension artérielle, Centre Hospitalier Annecy Genevois, Épagny Metz-Tessy, France
| |
Collapse
|
|
3
|
Wang P, Wu D, Gong Z, Adu-Gyamfi M, Kamhieh-Milz J, da Fonseca DLM, Sürücü G, Ashraf MI, Heidecke H, Sikorska D, Cabral-Marques O, Moll G, Riemekasten G, Witowski J, Catar R. Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis. Clin Immunol 2025; 273:110454. [PMID: 39956166 DOI: 10.1016/j.clim.2025.110454] [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: 10/04/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
Here, we investigate how autoantibodies against G protein-coupled receptors (GPCRs) on endothelial cells, which are present in patients with scleroderma renal crisis (SRC) impact on endothelin-1 (ET-1) production in human microvascular endothelial cells (HMECs). To this end, serum IgG fraction was isolated from SRC patients and applied to HMECs in culture. Compared to cells treated with either plain control medium or serum IgG from healthy individuals, exposure of HMECs to SRC-IgG resulted in a time- and concentration-dependent increase in ET-1 expression and release. This effect could be blocked by the protease activated receptor 1 (PAR1) inhibitor and mimicked by thrombin, the PAR1 activator. Transcription factor C-FOS/AP-1 and tissue factor (TF) were identified as mediators of these responses. Thus, it can be concluded that serum IgG fraction from SRC patients stimulates endothelial cells to produce ET-1, acting through PAR1 in cooperation with TF.
Collapse
Affiliation(s)
- Pinchao Wang
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Dashan Wu
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Zexian Gong
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Adu-Gyamfi
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Julian Kamhieh-Milz
- Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Gülistan Sürücü
- Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Muhammad I Ashraf
- Department of Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Dorota Sikorska
- Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Otavio Cabral-Marques
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo, Sao Paulo, SP, Brazil; Instituto D'Or de Ensino e Pesquisa, Sao Paulo, Brazil
| | - Guido Moll
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies and Berlin-Brandenburg, School for Regenerative Therapies and Julius Wolff Institute, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Gabriela Riemekasten
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
| | - Janusz Witowski
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.
| | - Rusan Catar
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
| |
Collapse
|
|
4
|
Kante A, Legendre P, Joly BS, Dunogué B, Hertig A, Terrier B, Massolin E, Coppo P, Ackermann F, Piccoli GB, Mouthon L, Guibourdenche J, Chaigne B. Pilot Study of Diagnostic Performances of Vascular Biomarkers Soluble fms-Like Tyrosine Kinase and Placental Growth Factor in Scleroderma Renal Crisis. Kidney Int Rep 2025; 10:866-876. [PMID: 40225361 PMCID: PMC11993226 DOI: 10.1016/j.ekir.2024.12.025] [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: 11/25/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 04/15/2025] Open
Abstract
Introduction Scleroderma renal crisis (SRC) is a major vascular complication of systemic sclerosis (SSc), associated with high morbidity and mortality. In this retrospective study, we evaluated the potential prognostic and diagnostic roles of angiogenesis molecules, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt1/PlGF ratio as biomarkers in SRC. Methods Sera samples from 27 patients with a history of SRC (SSc-SRC+) were collected following event occurence. Biomarker levels were assessed using an electrochemiluminescence immunoassay and compared with age- and sex-matched patients with SSc-SRC- (n = 24), hemolytic uremic syndrome (HUS) (n = 27), malignant hypertension (MHT) (n = 22), and donors (n = 61). Areas under the receiver-operating-characteristic curves (AUC) were used to evaluate diagnostic accuracy. Long-term dialysis risk was evaluated using a Cox model. Results The median (interquartile range [IQR]) PlGF (pg/ml) was significantly higher in the serum of patients with SSc-SRC+ (42.1 [21.4-51.8]) compared with donors (14.7 [11.8-17.9]), those with SSc-SRC- (18.5 [14.7-21.5]) (P < 0.0001), those with HUS (22.8 [19.5-29.6]), and those with MHT (25.5 [17.2-39.3]) (P < 0.0001). In a multivariate regression adjusting for multiple confounders, PlGF was associated with higher SRC risk with an odds ratio of 1.08 [1.01-1.22], (P = 0.034). A PlGF level above 24.5 pg/ml revealed an AUC of 0.81 (confidence interval [0.68-0.94]), a specificity of 95%, and a sensitivity of 67% for SRC diagnosis. Eleven patients with SSc-SRC+ reached end-stage kidney failure with significantly higher PlGF (42.9 [22.4-78.2]) compared with patients who were dialysis-free (19.7 [15.6-29.7], P = 0.03). Conclusion Serum PlGF may identify the risk of SRC occurrence among patients with SSc with a good specificity and represents a potential tool for long-term dialysis risk evaluation.
Collapse
Affiliation(s)
- Aïcha Kante
- Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
- Sorbonne Université, Paris, France
| | - Paul Legendre
- Service d’Immunologie clinique, Centre hospitalier du Mans, Le Mans, France
| | - Bérangère S. Joly
- Service d’Hématologie Biologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris (APHP Nord), Université Paris Cité, Paris, France
- INSERM UMRS-1138, Équipe 16, Centre de Recherche des Cordeliers, Université Paris Cité, Paris, France
- Centre National de Référence des Microangiopathies Thrombotiques, Paris, France
| | - Bertrand Dunogué
- Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
| | | | - Benjamin Terrier
- Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
| | - Elodie Massolin
- UF d'Hormonologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France
| | - Paul Coppo
- INSERM UMRS-1138, Équipe 16, Centre de Recherche des Cordeliers, Université Paris Cité, Paris, France
- Centre National de Référence des Microangiopathies Thrombotiques, Paris, France
- Service d'Hématologie, Hôpital Saint-Antoine, AP-HP, Paris, France
| | | | | | - Luc Mouthon
- Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
| | - Jean Guibourdenche
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
- UF d'Hormonologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France
| | - Benjamin Chaigne
- Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
- APHP-CUP, Hôpital Cochin, Université Paris Cité, Paris, France
| |
Collapse
|
|
5
|
Maltez N, Wang M, Wells GA, Tugwell P, Baron M, Marjanovic Z, Lansiaux P, Farge D, Hudson M. Improvement in Skin Fibrosis and Lung Function with Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis. Transplant Cell Ther 2025:S2666-6367(25)01011-5. [PMID: 39938806 DOI: 10.1016/j.jtct.2025.02.005] [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: 09/06/2024] [Revised: 01/21/2025] [Accepted: 02/04/2025] [Indexed: 02/14/2025]
Abstract
Systemic sclerosis (SSc) is a severe, progressive disease with limited treatment options. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to be an effective treatment for rapidly progressive SSc. The objective of this study was to evaluate the effectiveness of AHSCT for SSc compared to real-world clinical care. SSc patients from France who underwent AHSCT were compared to patients from Canada who met criteria for AHSCT (as defined in the ASTIS trial) but received conventional care. The primary outcome was overall survival. Secondary outcomes included modified Rodnan skin score (mRSS) and forced vital capacity (FVC). Overall survival was estimated by Kaplan-Meier survival curves. Measures of mRSS and FVC were compared using linear regression models. Analyses were adjusted for baseline scores and incorporated stabilized inverse probability of treatment weights to account for confounding by indication. Propensity scores were estimated using logistic regression. Forty-one AHSCT patients and 85 conventional care patients were compared. AHSCT was associated with a suggestive, though not statistically significant trend toward improvement in overall survival (log-rank P = .115). In follow-up, the mRSS was lower with AHSCT compared to conventional care: between group difference of 8.81; P ≤ .0001 at 12 months and 11.28; P = .011 at 60 months. There was no significant difference in FVC between groups at 12 months but at 24 months, AHSCT was associated with a higher FVC (between group difference of 10.53 (P = .05)). This study demonstrates with real-world long-term data that compared with conventional care, treatment with AHSCT may offer superior outcomes for SSc patients.
Collapse
Affiliation(s)
- Nancy Maltez
- School of Epidemiology and Public Health, University of Ottawa, The Ottawa Hospital, Division of Rheumatology, Ottawa, Canada.
| | | | - Georges A Wells
- Cardiovascular Research Methods Centre, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Peter Tugwell
- School of Epidemiology and Public Health, University of Ottawa, The Ottawa Hospital, Division of Rheumatology, Ottawa, Canada
| | - Murray Baron
- McGill University, Jewish General Hospital, Montreal, Canada
| | | | - Pauline Lansiaux
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, Centre de Référence des Maladies auto-immunes systémiques Rares d'Ile-de-France, AP-HP, Hôpital St-Louis, Paris, France
| | - Dominique Farge
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, Centre de Référence des Maladies auto-immunes systémiques Rares d'Ile-de-France, AP-HP, Hôpital St-Louis, Paris, France
| | - Marie Hudson
- Lady Davis Institute, McGill University, Jewish General Hospital, Montreal, Canada
| |
Collapse
|
|
6
|
Kotani H, Matsuda KM, Yamaguchi K, Ono C, Kogo E, Ogawa K, Kobayashi Y, Hisamoto T, Kawanabe R, Kuzumi A, Fukasawa T, Yoshizaki‐Ogawa A, Goshima N, Sato S, Yoshizaki A. Diversity and Epitope Spreading of Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement. Arthritis Rheumatol 2025; 77:67-79. [PMID: 39219033 PMCID: PMC11684998 DOI: 10.1002/art.42975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/07/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVE Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti-RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc). METHODS We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full-length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell-free translation system. Subsequently, we prepared antigen-binding plates and measured autoantibodies in the serum of patients with SSc. RESULTS Autoantibodies against different RNAP III complex subunits were found in patients who were ARA-positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein-D, a biomarker of interstitial lung disease. However, the extent of disease on high-resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker. CONCLUSION Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity.
Collapse
Affiliation(s)
| | | | | | | | - Emi Kogo
- ProteoBridge CorporationKoto‐kuJapan
| | | | | | | | | | | | | | | | - Naoki Goshima
- ProteoBridge Corporation and the University of MusashinoKoto‐kuJapan
| | | | | |
Collapse
|
|
7
|
Wajid S, Shapiro L, Farrukh L, Hu K, Feustel PJ, Hongalgi K, Mehta S. Acute Kidney Injury in Systemic Sclerosis Beyond Scleroderma Renal Crisis: A Case-Control Study. J Clin Rheumatol 2024; 30:219-222. [PMID: 38980171 DOI: 10.1097/rhu.0000000000002108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
BACKGROUND AND OBJECTIVES Renal involvement in systemic sclerosis remains a significant concern with the focus often centered on scleroderma renal crisis (SRC). However, the broader spectrum of renal manifestations, beyond SRC, remains underrecognized. In our case-control analysis, we describe other causes, risk factors, and renal outcomes of acute kidney injury (AKI) in systemic sclerosis other than SRC. METHODS Patients diagnosed with SSC, with and without AKI, between 2017 and 2023 at Albany Medical Center, were included in the case-control study using International Classification of Diseases , 10th Revision codes and electronic medical records. Patients with SRC were carefully excluded. Data were collected and compared between AKI and non-AKI groups for patients' demographics, clinical characteristics, and baseline treatment. Additionally, data were collected for baseline, peak, and follow-up creatinine, etiology of AKI, treatment, and outcomes. Statistical analysis was performed using R (version 4.3.0) and Minitab (V19). Categorical variables were presented as frequencies/percentages, and continuous variables as means/standard deviations. Associations between categorical variables were assessed by χ 2 test and Fisher exact test. Odds ratios and 95% confidence intervals were calculated using binary logistic regression to separately assess the effect of each independent variable on the odds of AKI. Statistical significance was set at p < 0.05. RESULTS A total of 74 cases were identified. Out of these 74 cases, 27 had AKI and 47 did not have AKI. Out of the 27 AKI cases, 4 with SRC were excluded. Advanced age, chronic kidney disease, and heart failure were identified as risk factors for AKI development. The predominant cause of AKI was prerenal etiology, accounting for 47.8% (n = 11) of cases. This was followed by cardiorenal syndrome and acute tubular necrosis, accounting for 21.7% and 17.3% of the cases, respectively. Most of the cases with AKI had complete renal recovery 78% (n = 18), whereas 17% (n = 4) had progression of the underlying chronic kidney disease. One patient progressed to end-stage renal disease requiring hemodialysis. CONCLUSIONS This analysis highlights the risk factors and variable clinicopathological courses of renal involvement in patients with scleroderma. This may range from mild AKI with good prognosis to life-threatening SRC.
Collapse
Affiliation(s)
- Sumbal Wajid
- From the Department of Medicine, Albany Medical Center, Albany, NY
| | - Lee Shapiro
- From the Department of Medicine, Albany Medical Center, Albany, NY
| | - Larabe Farrukh
- From the Department of Medicine, Albany Medical Center, Albany, NY
| | - Kurt Hu
- Department of Pulmonary and Critical Care Medicine, Froedtert and the Medical College of Wisconsin, Milwaukee, WI
| | - Paul J Feustel
- Department of Research Affairs, Albany Medical College, Albany, NY
| | | | - Swati Mehta
- From the Department of Medicine, Albany Medical Center, Albany, NY
| |
Collapse
|
|
8
|
Tong X, He H, Ning Z, Shen R, Du C, Zeng X, Wang Q, He ZX, Xu D, Zhao X. Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging. Magn Reson Imaging 2024; 109:203-210. [PMID: 38513788 DOI: 10.1016/j.mri.2024.03.025] [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: 10/12/2023] [Revised: 03/09/2024] [Accepted: 03/18/2024] [Indexed: 03/23/2024]
Abstract
PURPOSE To determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. MATERIAL AND METHODS Forty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. RESULTS Compared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. CONCLUSION Multi-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.
Collapse
Affiliation(s)
- Xinyu Tong
- Department of Nuclear Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Huilin He
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Zihan Ning
- Center for Biomedical Imaging Research, School of Biomedical Engineering, Tsinghua University, Beijing, China
| | - Rui Shen
- Center for Biomedical Imaging Research, School of Biomedical Engineering, Tsinghua University, Beijing, China
| | - Chenlin Du
- Center for Biomedical Imaging Research, School of Biomedical Engineering, Tsinghua University, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Zuo-Xiang He
- Department of Nuclear Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
| | - Dong Xu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.
| | - Xihai Zhao
- Center for Biomedical Imaging Research, School of Biomedical Engineering, Tsinghua University, Beijing, China.
| |
Collapse
|
|
9
|
Możdżan M, Węgiel A, Biskup L, Brzezińska O, Makowska J. Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern? J Clin Med 2024; 13:3022. [PMID: 38892733 PMCID: PMC11172938 DOI: 10.3390/jcm13113022] [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: 04/15/2024] [Revised: 05/10/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Systemic sclerosis (SSc) represents a rare and intricate autoimmune connective tissue disease, the pathophysiology of which has not been fully understood. Its key features include progressive fibrosis of the skin and internal organs, vasculopathy and aberrant immune activation. While various anti-nuclear antibodies can serve as biomarkers for the classification and prognosis of SSc, their direct role in organ dysfunction remains unclear. Anti-Th/To antibodies are present in approximately 5% of SSc patients, and are particularly prevalent among those with the limited subtype of the disease. Although the presence of these autoantibodies is associated with a mild course of the disease, there is a strong connection between them and severe clinical manifestations of SSc, including interstitial lung disease, pulmonary arterial hypertension and gastrointestinal involvement. Also, the additional clinical correlations, particularly with malignancies, need further research. Moreover, the disease's course seems to be influenced by antibodies, specific serum cytokines and TLR signaling pathways. Understanding the relationships between presence of anti-Th/To, its molecular aspects and response to treatment options is crucial for the development of novel, personalized therapeutic techniques and should undergo profound analysis in future studies.
Collapse
Affiliation(s)
- Maria Możdżan
- Department of Rheumatology, Medical University of Lodz, 90-549 Lodz, Poland; (A.W.); (L.B.); (O.B.)
| | | | | | | | - Joanna Makowska
- Department of Rheumatology, Medical University of Lodz, 90-549 Lodz, Poland; (A.W.); (L.B.); (O.B.)
| |
Collapse
|
|
10
|
Pethő Á, Fintha A, Kardos M. An unusual complication of kidney biopsy: a case report. J Med Case Rep 2024; 18:41. [PMID: 38308348 PMCID: PMC10837957 DOI: 10.1186/s13256-023-04338-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/26/2023] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND The kidney biopsy is a routine procedure. Once an indication has been established, the benefit-risk balance may be considered. Sometimes, even with effective treatment, a severe complication may develop. CASE PRESENTATION We present the case of a Caucasian 20-year-old young woman admitted to investigating and treating acute kidney injury. Renal involvement was characterized by kidney damage requiring hemodialysis treatment, positive immunologic testing, 0.5 g/day proteinuria, and microscopic hematuria. Contraindications were excluded, so an ultrasound-guided kidney biopsy was performed. To reduce the bleeding complication, Octostim (desmopressin) was administered. There were no direct complications following the kidney biopsy, so we continued the immunosuppressive treatment. Histologically founded thrombotic microangiopathy. However, 1 week later, severe bleeding developed with the need for urgent surgical left kidney removal. CONCLUSION Kidney biopsy can be considered a routine procedure, and various bleeding episodes are most common in terms of complications, the detection of which is essential. Delayed bleeding complications are rare and can be caused by minor injuries. Our young patient had no injury during the hospitalization. We hypothesized that the developed serious and delayed bleeding complication resulted from effective immunosuppressive treatment. To the best of our knowledge, this is the first such case to date. However, renal biopsy in the case of thrombotic microangiopathy requires caution.
Collapse
Affiliation(s)
- Ákos Pethő
- Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
| | - Attila Fintha
- Faculty of Medicine, Department of Pathology and Cancer Research, Semmelweis University, Budapest, Hungary
| | - Magdolna Kardos
- Institute of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| |
Collapse
|
|
11
|
Silva-Velasco DL, Cervantes-Pérez LG, Sánchez-Mendoza A. ACE inhibitors and their interaction with systems and molecules involved in metabolism. Heliyon 2024; 10:e24655. [PMID: 38298628 PMCID: PMC10828069 DOI: 10.1016/j.heliyon.2024.e24655] [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: 02/28/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 02/02/2024] Open
Abstract
The main function of the renin-angiotensin-aldosterone system (RAAS) is the regulation of blood pressure; therefore, researchers have focused on its study to treat cardiovascular and renal diseases. One of the most widely used treatments derived from the study of RAAS, is the use of angiotensin-converting enzyme inhibitors (ACEi). Since it was discovered, the main target of ACEi has been the cardiovascular and renal systems. However, being the RAAS expressed locally in several specialized tissues and cells such as pneumocytes, hepatocytes, spleenocytes, enterocytes, adipocytes, and neurons the effect of inhibitors has expanded, because it is expected that RAAS has a role in the specific function of those cells. Many chronic degenerative diseases compromise the correct function of those organs, and in most of them, the RAAS is overactivated. Therefore, the use of ACEi must exert a benefit on an impaired system. Accordingly, the objective of this review is to present a brief overview of the cardiovascular and renal actions of ACEi and its effects in organs that are not the classic targets of ACEi that carry on glucose and lipid metabolism.
Collapse
Affiliation(s)
| | - Luz G. Cervantes-Pérez
- Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Alicia Sánchez-Mendoza
- Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| |
Collapse
|
|
12
|
Mehdipour Dalivand M, Hadjiabbasi A, Ramezanzadeh E, Habibzadeh SM, Goudarzi K, Shahriarirad R, Zayeni H. Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report. J Med Case Rep 2024; 18:32. [PMID: 38225664 PMCID: PMC10790409 DOI: 10.1186/s13256-023-04273-6] [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: 07/12/2023] [Accepted: 11/17/2023] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Systemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma. CASE PRESENTATION A 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises. CONCLUSION SSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.
Collapse
Affiliation(s)
- Mahsa Mehdipour Dalivand
- Rheumatology Research Center, Department of Internal Medicine, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Asghar Hadjiabbasi
- Guilan Rheumatology Research Center, Department of Rheumatology, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Elham Ramezanzadeh
- Guilan Nephrology Research Center, Department of Nephrology, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Kimia Goudarzi
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Shahriarirad
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Habib Zayeni
- Rheumatology Research Center, Department of Internal Medicine, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
13
|
Cordoba-Hurtado AM, Fuentes-Mendez L, Perez-Navarro LM, Soto-Abraham V, Valdez-Ortiz R. Overlap Syndrome of Diffuse Systemic Sclerosis, Sjögren Syndrome, and ANCA-Associated Renal-Limited Vasculitis: Three Entities in One Patient - Case Report. Case Rep Nephrol Dial 2024; 14:48-55. [PMID: 38524730 PMCID: PMC10959543 DOI: 10.1159/000537873] [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: 09/20/2023] [Accepted: 02/13/2024] [Indexed: 03/26/2024] Open
Abstract
Introduction The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment.
Collapse
|
|
14
|
Dumas G, Arabi YM, Bartz R, Ranzani O, Scheibe F, Darmon M, Helms J. Diagnosis and management of autoimmune diseases in the ICU. Intensive Care Med 2024; 50:17-35. [PMID: 38112769 DOI: 10.1007/s00134-023-07266-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 11/01/2023] [Indexed: 12/21/2023]
Abstract
Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.
Collapse
Affiliation(s)
- Guillaume Dumas
- Medical Intensive Care Unit, Service de Médecine Intensive-Réanimation, CHU Grenoble-Alpes, Université Grenoble-Alpes, INSERM, U1042-HP2, Grenoble, France.
| | - Yaseen M Arabi
- Intensive Care Department, Ministry of the National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences Riyadh, Riyadh, Kingdom of Saudi Arabia
| | - Raquel Bartz
- Department of Anesthesia, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Otavio Ranzani
- Barcelona Institute for Global Health, ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
- Pulmonary Division, Faculdade de Medicina, Heart Institute, InCor, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Franziska Scheibe
- Department of Neurology and Experimental Neurology, Charité- Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
- NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Michaël Darmon
- Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA Team, and Clinical EpidemiologyUMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Université Paris Cité, Paris, France
| | - Julie Helms
- Faculté de Médecine, Service de Médecine Intensive-Réanimation, Université de Strasbourg (UNISTRA), Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1 Place de L'Hôpital, Strasbourg, France
| |
Collapse
|
|
15
|
Sanada H, Hara S, Horita M, Kawahara H, Yoshida M, Takahashi Y, Tsuge S, Zoshima T, Nishioka R, Ito K, Mizushima I, Matsushita T, Kawano M. De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report. BMC Nephrol 2023; 24:355. [PMID: 38049714 PMCID: PMC10696825 DOI: 10.1186/s12882-023-03416-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 11/28/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. CASE PRESENTATION We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. CONCLUSIONS SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.
Collapse
Affiliation(s)
- Hajime Sanada
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Satoshi Hara
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan.
| | - Makoto Horita
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Hiroyuki Kawahara
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Misaki Yoshida
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Yoshinori Takahashi
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Shunsuke Tsuge
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Takeshi Zoshima
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Ryo Nishioka
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Kiyoaki Ito
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Ichiro Mizushima
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| | - Takashi Matsushita
- Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Kanazawa University Hospital, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan
| |
Collapse
|
|
16
|
Portocarrero JP, Tawhari I, Ghossein C. Kidney Transplant Outcomes in Patients With Scleroderma an Experience at Northwestern Memorial Hospital, Chicago, Illinois. Transplant Proc 2023; 55:2410-2413. [PMID: 37923572 DOI: 10.1016/j.transproceed.2023.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 08/15/2023] [Accepted: 09/22/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND Scleroderma renal crisis (SRC) is a devastating complication of diffuse cutaneous systemic sclerosis (dcSSc) that occurs in 5% to 20% of patients in this population. End-stage kidney disease develops in 25% to 40% of SRC, and mortality occurs in 50% at 5 years. Kidney transplantation (KT) is a viable option, but little data exist on outcomes. METHODS We performed a retrospective study of all patients with dcSSc who underwent KT at Northwestern Hospital between 2000 and 2020. The objective of this study was to determine graft and patient survival at years 5 and 10 post-transplant. RESULTS Both patient and graft survival were 78% and 100% at 5 and 10 years, respectively. Kidney transplantation is associated with favorable outcomes in patients and graft survival at 5 and 10 years in patients with dcSSc.
Collapse
Affiliation(s)
| | | | - Cybele Ghossein
- Northwestern University Feinberg School of Medicine, Chicago, IL
| |
Collapse
|
|
17
|
Zhang Y, Yang Y, Gao X, Gao W, Zhang L. Research progress on mesenchymal stem cells and their exosomes in systemic sclerosis. Front Pharmacol 2023; 14:1263839. [PMID: 37693906 PMCID: PMC10485262 DOI: 10.3389/fphar.2023.1263839] [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: 07/20/2023] [Accepted: 08/15/2023] [Indexed: 09/12/2023] Open
Abstract
Systemic sclerosis (SSc) is a connective tissue disease with an unknown etiology. Clinically, it is characterized by localized or diffuse skin thickening and fibrosis. The pathogenesis of SSc includes microvascular injury, autoimmune-mediated inflammation, and fibroblast activation. These processes interact and contribute to the diverse clinicopathology and presentation of SSc. Given the limited effectiveness and substantial side effects of traditional treatments, the treatment strategy for SSc has several disadvantages. Mesenchymal stem cells (MSCs) are expected to serve as effective treatment options owing to their significant immunomodulatory, antifibrotic, and pro-angiogenic effects. Exosomes, secreted by MSCs via paracrine signaling, mirror the effect of MSCs as well as offer the benefit of targeted delivery, minimal immunogenicity, robust reparability, good safety and stability, and easy storage and transport. This enables them to circumvent the limitations of the MSCs. When using exosomes, it is crucial to consider preparation methods, quality standards, and suitable drug delivery systems, among other technical issues. Therefore, this review aims to summarize the latest research progress on MSCs and exosomes in SSc, offering novel ideas for treating SSc.
Collapse
Affiliation(s)
| | | | | | | | - Liyun Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| |
Collapse
|
|
18
|
Aterini L, Gallo M, Vadalà B, Aterini S. Thrombotic Microangiopathy and Multiple Organ Failure in Scleroderma Renal Crisis: A Case Report. Cureus 2023; 15:e44322. [PMID: 37779794 PMCID: PMC10538352 DOI: 10.7759/cureus.44322] [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] [Accepted: 08/29/2023] [Indexed: 10/03/2023] Open
Abstract
This case report can be considered a rare occurrence of scleroderma renal crisis (SRC) presenting with a severe clinical course and multiple organ failure. A patient diagnosed with systemic sclerosis four years earlier was admitted to the hospital because of severe malignant systolic-diastolic arterial hypertension and acute kidney injury (AKI). Exacerbating disease suggested thrombotic microangiopathy (TMA) and the PLASMIC (Platelet count; combined hemoLysis variable; absence of Active cancer; absence of Stem-cell or solid-organ transplant; MCV; INR; Creatinine) score was used in the differential diagnosis. Despite the timely initiation of therapy with ACE inhibitors (ACE-I), the progressive renal failure required hemodialysis treatment, but renal function never recovered. Disease duration, skin involvement, and previous specific pharmacological therapy represented multiple risk factors that determined a clinical course complicated by pericardial tamponade with acute heart failure, acute pancreatitis, and ischemic stroke, with fatal evolution. These complications presented a challenging clinical sequence of events requiring an interdisciplinary course of action. Timely ascertainment of the SRC is important given the possible severe organ involvement as well as mortality. A diagnosis of scleroderma renal crisis should be considered in cases of acute kidney injury associated with known risk factors. Early treatment and collaboration between rheumatology and renal physicians can improve patient outcomes.
Collapse
Affiliation(s)
- Lorenzo Aterini
- Nephrology, AOU (Azienda Ospedaliera Universitaria) Meyer Children Hospital, School of Human Health Sciences at University of Firenze, Firenze, ITA
| | - Marco Gallo
- Hemodialysis Centre, Istituto Fiorentino di Cura e Assistenza (IFCA), Firenze, ITA
| | - Barbara Vadalà
- Hemodialysis Centre, Istituto Fiorentino di Cura e Assistenza (IFCA), Firenze, ITA
| | - Stefano Aterini
- Hemodialysis Centre, Istituto Fiorentino di Cura e Assistenza (IFCA), Firenze, ITA
| |
Collapse
|
|
19
|
Yen TH, Chen JP, Hsieh TY, Hung WT, Lai KL, Hsieh CW, Chen HH, Huang WN, Chen YH, Chen YM. The diagnostic and prognostic value of a line immunoblot assay in Taiwanese patients with systemic sclerosis. Clin Chim Acta 2023:117457. [PMID: 37390945 DOI: 10.1016/j.cca.2023.117457] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 05/23/2023] [Accepted: 06/26/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND AND AIMS We aimed to evaluate the diagnostic performance and prognostic value of disease-specific antibodies and anti-Ro52 using a commercial line immunoblot assay (LIA) in Taiwanese patients with systemic sclerosis (SSc). MATERIALS AND METHODS We retrospectively enrolledall individuals at the Taichung Veterans General Hospital. We evaluated the diagnostic performance of LIA, anti-nuclear antibody (ANA) by indirect immunofluorescence (IIF) and also the association between the autoantibodies and the clinical phenotype using multivariable logistic regression. RESULTS The LIA exhibited a sensitivity of 65.4% and a specificity of 65.4%, at the optimal cutoff values of 2+ signal intensity. By taking the result of ANA into consideration, the optimal cutoff point was redefined as 1+. We observed a higher risk of diffuse cutaneous SSc (dcSSc) in those with negative autoantibodies, positive anti-Scl-70, anti-RNA polymerase III, and anti-Ro-52. Interstitial lung disease (ILD) was associated with negative autoantibodies, and positive anti-Scl-70 and anti-Ro52. Anti-Ro52 positivity was also associated with pulmonary arterial hypertension (PAH) and gastrointestinal tract involvement. CONCLUSION The presence of anti-Ro52 or the absence of SSc-specific autoantibodies may potentially indicate advanced diseases in patients with SSc. The incorporation of both IIF and LIA testing may improve the diagnostic specificity of SSc.
Collapse
Affiliation(s)
- Tsai-Hung Yen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Peng Chen
- Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan
| | - Tsu-Yi Hsieh
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Wei-Ting Hung
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Kuo-Lung Lai
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Chia-Wei Hsieh
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Hsin-Hua Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Nan Huang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hsing Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Ming Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
| |
Collapse
|
|
20
|
Luan X, Zhang X, Nie M, Zhao Y. Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment. RESEARCH (WASHINGTON, D.C.) 2023; 6:0141. [PMID: 37228639 PMCID: PMC10204745 DOI: 10.34133/research.0141] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 04/17/2023] [Indexed: 05/27/2023]
Abstract
Traditional Chinese medicine, such as Tripterygium wilfordii and Paeonia lactiflora, has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.
Collapse
Affiliation(s)
- Xi Luan
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xiaoxuan Zhang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Min Nie
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yuanjin Zhao
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| |
Collapse
|
|
21
|
Scheen M, Dominati A, Olivier V, Nasr S, De Seigneux S, Mekinian A, Issa N, Haidar F. Renal involvement in systemic sclerosis. Autoimmun Rev 2023; 22:103330. [PMID: 37031831 DOI: 10.1016/j.autrev.2023.103330] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 04/03/2023] [Indexed: 04/11/2023]
Abstract
Systemic sclerosis is a rare autoimmune vasculopathy associated with dysregulated innate and adaptive immunity that leads to generalized systemic fibrosis. Renal involvement occurs in a significant proportion of systemic sclerosis patients, and is associated with worse outcome. Scleroderma renal crisis (SRC) is the most studied and feared renal complication described in systemic sclerosis. However, with the emergence of ACE inhibitors and better management, the mortality rate of SRC has significantly decreased. Renal disease in systemic sclerosis offers a wide array of differential diagnoses that may be challenging for the clinician. The spectrum of renal manifestations in systemic sclerosis ranges from an isolated decrease in glomerular filtration rate, increased intrarenal arterial stiffness, and isolated proteinuria due to SRC to more rare manifestations such as association with antiphospholipid antibody nephropathy and ANCA-associated vasculitis. The changes observed in the kidneys in systemic sclerosis are thought to be due to a complex interplay of various factors, including renal vasculopathy, as well as the involvement of the complement system, vasoactive mediators such as endothelin-1, autoimmunity, prothrombotic and profibrotic cytokines, among others. This literature review aims to provide an overview of the main renal manifestations in systemic sclerosis by discussing the most recent epidemiological and pathophysiological data available and the challenges for clinicians in making a diagnosis of renal disease in patients with systemic sclerosis.
Collapse
Affiliation(s)
- Marc Scheen
- Hôpitaux Universitaires de Genève, Service de Néphrologie, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland.
| | - Arnaud Dominati
- Hôpitaux Universitaires de Genève, Service d'allergologie et immunologie, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland
| | - Valérie Olivier
- Hôpitaux Universitaires de Genève, Service de Néphrologie, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland
| | - Samih Nasr
- Mayo Clinic College of Medicine and Science, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Sophie De Seigneux
- Hôpitaux Universitaires de Genève, Service de Néphrologie, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland
| | - Arsène Mekinian
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne, 75012 Paris, France
| | - Naim Issa
- Mayo Clinic College of Medicine and Science, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Fadi Haidar
- Hôpitaux Universitaires de Genève, Service de Néphrologie, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland
| |
Collapse
|
|
22
|
Lee AI, Heidari P, Fenves AZ, Bardia A, Ta R. Case 8-2023: A 71-Year-Old Woman with Refractory Hemolytic Anemia. N Engl J Med 2023; 388:1032-1041. [PMID: 36920760 PMCID: PMC10133839 DOI: 10.1056/nejmcpc2211370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Affiliation(s)
- Alfred I Lee
- From the Department of Medicine, Yale School of Medicine, New Haven, CT (A.I.L.); and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Massachusetts General Hospital, and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Harvard Medical School - both in Boston
| | - Pedram Heidari
- From the Department of Medicine, Yale School of Medicine, New Haven, CT (A.I.L.); and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Massachusetts General Hospital, and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Harvard Medical School - both in Boston
| | - Andrew Z Fenves
- From the Department of Medicine, Yale School of Medicine, New Haven, CT (A.I.L.); and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Massachusetts General Hospital, and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Harvard Medical School - both in Boston
| | - Aditya Bardia
- From the Department of Medicine, Yale School of Medicine, New Haven, CT (A.I.L.); and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Massachusetts General Hospital, and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Harvard Medical School - both in Boston
| | - Robert Ta
- From the Department of Medicine, Yale School of Medicine, New Haven, CT (A.I.L.); and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Massachusetts General Hospital, and the Departments of Radiology (P.H.), Medicine (A.Z.F., A.B.), and Pathology (R.T.), Harvard Medical School - both in Boston
| |
Collapse
|
|
23
|
Zhang X, Zhang H, Zhao J, Li Y, Wang H, Li C. Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study. Clin Rheumatol 2023; 42:1297-1306. [PMID: 36604358 DOI: 10.1007/s10067-022-06487-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 12/10/2022] [Accepted: 12/12/2022] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). METHODS A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2 years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. RESULTS The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud's phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). CONCLUSIONS This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.
Collapse
Affiliation(s)
- Xiaoying Zhang
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Huijuan Zhang
- Department of Rheumatology, She Xian Hospital, Handan, Hebei Province, China
| | - Jing Zhao
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Yun Li
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Hongyan Wang
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China
| | - Chun Li
- Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South St., Beijing, 100044, China.
| |
Collapse
|
|
24
|
Foocharoen C, Tonsawan P, Pongkulkiat P, Anutrakulchai S, Mahakkanukrauh A, Suwannaroj S. Management review of scleroderma renal crisis: An update with practical pointers. Mod Rheumatol 2023; 33:12-20. [PMID: 35349704 DOI: 10.1093/mr/roac028] [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: 01/11/2022] [Revised: 02/20/2022] [Accepted: 03/14/2022] [Indexed: 01/05/2023]
Abstract
Scleroderma renal crisis (SRC) represents severe, fatal internal organ involvement brought on by systemic sclerosis. A high rate of renal replacement therapy and mortality persists despite various treatments. Depending on the stage of SRC, a vasodilator called angiotensin-converting enzyme inhibitor is the treatment of choice. The efficacy of various other vasodilators (i.e. endothelin-1 receptor antagonist) and complement cascade blocker for SRC have been investigated; however, no randomized control trial has been conducted. A new approach has been proposed for the management of SRC, categorized by specific clinical features of narrowly defined SRC and systemic sclerosis-thrombotic microangiopathy. SRC prophylaxis using angiotensin-converting enzyme inhibitor might be harmful, leading to a poor renal outcome, so the pathogenesis of SRC needs to be clarified in order to identify other possible preventions or therapies.
Collapse
Affiliation(s)
- Chingching Foocharoen
- Department of Medicine, Division of Rheumatology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Pantipa Tonsawan
- Department of Medicine, Division of Nephrology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Patnarin Pongkulkiat
- Department of Medicine, Division of Rheumatology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sirirat Anutrakulchai
- Department of Medicine, Division of Nephrology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ajanee Mahakkanukrauh
- Department of Medicine, Division of Rheumatology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Siraphop Suwannaroj
- Department of Medicine, Division of Rheumatology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| |
Collapse
|
|
25
|
Horino T, Terada Y. Postpartum scleroderma renal crisis with renal thrombotic microangiopathy. QJM 2022; 116:390-392. [PMID: 36515495 DOI: 10.1093/qjmed/hcac275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Affiliation(s)
- Taro Horino
- Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Yoshio Terada
- Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| |
Collapse
|
|
26
|
Hughes M, Allanore Y, Baron M, Del Galdo F, Denton CP, Frech T, Furst DE, Galetti I, Dagna L, Herrick AL, Kuwana M, Matucci-Cerinic P, McMahan ZH, Murray CD, Proudman S, Matucci-Cerinic M. Proton pump inhibitors in systemic sclerosis: a reappraisal to optimise treatment of gastro-oesophageal reflux disease. THE LANCET. RHEUMATOLOGY 2022; 4:e795-e803. [PMID: 37936680 PMCID: PMC10628971 DOI: 10.1016/s2665-9913(22)00183-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Gastroesophageal reflux disease (GERD) is associated with significant morbidity in patients with systemic sclerosis (SSc). Although the introduction of proton pump inhibitors (PPIs) into clinical care have represented a major achievement in the management of oesophago-gastric problems in SSc, PPIs are seldom fully effective in SSc patients, and the utilization of maximum PPI dosages is a very frequent clinical practice. However, currently there is little evidence currently to support the empiric use of PPIs in SSc which is especially relevant in regard to safety concerns of long-term exposure with have been raised in the general population. The purpose of this viewpoint is to highlight the significant beneficial impact of PPIs on GERD in SSc, while considering the potential adverse effects in this patient population. Furthermore, we highlight the unmet needs of SSc patients with GERD, and also propose an agenda for future research to optimise the safe and effective use of PPIs in SSc.
Collapse
Affiliation(s)
- Michael Hughes
- Tameside Hospital, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, United Kingdom
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom
| | - Yannick Allanore
- Service de Rhumatologie, Hôpital Cochin, APHP, Université de Paris, Paris, France
| | - Murray Baron
- Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Francesco Del Galdo
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | - Christopher P Denton
- Centre for Rheumatology, Royal Free Campus, University College London, United Kingdom
| | - Tracy Frech
- Vanderbilt University Medical Center, Department of Medicine, Division of Rheumatology and Immunology, Nashville, TN, USA
| | - Daniel E Furst
- Department of Experimental and Clinical Medicine, University of Florence & Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
- Division of Rheumatology, Department of Medicine, University of California in Los Angeles, Los Angeles, California, USA
| | - Ilaria Galetti
- FESCA, Federation of European Scleroderma Associations, Belgium
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Ariane L Herrick
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom
- Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Pietro Matucci-Cerinic
- University Hospital, Santa Maria della Misericordia, Department of Surgery and Transplantation, University of Udine, Italy
| | - Zsuzsanna H McMahan
- Johns Hopkins University School of Medicine, Department of Medicine, Division of Rheumatology, Baltimore, MD
| | - Charles D Murray
- Jewish General Hospital, Division of Rheumatology, McGill University, Montreal, Canada
| | - Susanna Proudman
- Rheumatology Unit, Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, Adelaide, South Australia, 5000
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
- Dept. Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy
| |
Collapse
|
|
27
|
Gigante A, Leodori G, Pellicano C, Villa A, Rosato E. Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy. Am J Med Sci 2022; 364:529-537. [PMID: 35537505 DOI: 10.1016/j.amjms.2022.02.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 10/17/2021] [Accepted: 02/16/2022] [Indexed: 01/25/2023]
Abstract
The spectrum of kidney involvement in systemic sclerosis (SSc) includes scleroderma renal crisis, widely recognized as the most severe renal-vascular complication, but also several forms of chronic renal vasculopathy and reduced renal function are complications of scleroderma. Scleroderma renal crisis, myeloperoxidase-antineutrophil cytoplasmic antibody associated glomerulonephritis, penicillamine-associated renal disease, abnormal urinalysis, alteration of vascular endothelial markers, scleroderma associated-vasculopathy with abnormal renal resistance indices and cardiorenal syndromes type 5 were also reported in SSc patients. A frequent form of renal involvement in SSc patients is a subclinical renal vasculopathy, characterized by vascular damage and normal renal function. Indeed, asymptomatic renal changes, expressed by increase of intrarenal stiffness, are often non-progressive in SSc patients but can lead to a reduction in renal functional reserve. The purpose of this review is to provide an assessment of kidney involvement in SSc, from SRC to subclinical renal vasculopathy.
Collapse
Affiliation(s)
- Antonietta Gigante
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giorgia Leodori
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Chiara Pellicano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Annalisa Villa
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Edoardo Rosato
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
| |
Collapse
|
|
28
|
Jerjen R, Nikpour M, Krieg T, Denton CP, Saracino AM. Systemic sclerosis in adults. Part I: Clinical features and pathogenesis. J Am Acad Dermatol 2022; 87:937-954. [PMID: 35131402 DOI: 10.1016/j.jaad.2021.10.065] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/06/2021] [Accepted: 10/21/2021] [Indexed: 11/27/2022]
Abstract
Systemic sclerosis (SSc), also referred to as systemic scleroderma or scleroderma, is a rare, complex immune-mediated connective tissue disease characterized by progressive skin fibrosis and other clinically heterogenous features. The etiopathogenesis of SSc involves vasculopathy and immune system dysregulation occurring on a permissive genetic and epigenetic background, ultimately leading to fibrosis. Recent developments in our understanding of disease-specific autoantibodies and bioinformatic analyses has led to a reconsideration of the purely clinical classification of diffuse and limited cutaneous SSc subgroups. Autoantibody profiles are predictive of skin and internal organ involvement and disease course. Early diagnosis of SSc, with commencement of disease-modifying treatment, has the potential to improve patient outcomes. In SSc, many of the clinical manifestations that present early signs of disease progression and activity are cutaneous, meaning dermatologists can and should play a key role in the diagnosis and management of this significant condition. The first article in this continuing medical education series discusses the epidemiology, clinical characteristics, and pathogenesis of SSc in adults, with an emphasis on skin manifestations, the important role of dermatologists in recognizing these, and their correlation with systemic features and disease course.
Collapse
Affiliation(s)
- Rebekka Jerjen
- Department of Dermatology, The Alfred Hospital, Melbourne, Australia
| | - Mandana Nikpour
- Department of Rheumatology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Thomas Krieg
- Department Dermatology and Translational Matrix Biology, CMMC and CECAD, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Christopher P Denton
- Division of Medicine, Centre for Rheumatology and Connective Tissues Diseases, University College London, London, United Kingdom; Department of Rheumatology, Royal Free NHS Foundation Trust, London, United Kingdom
| | - Amanda M Saracino
- Department of Dermatology, The Alfred Hospital, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia.
| |
Collapse
|
|
29
|
Bellocchi C, Chung A, Volkmann ER. Predicting the Progression of Very Early Systemic Sclerosis: Current Insights. Open Access Rheumatol 2022; 14:171-186. [PMID: 36133926 PMCID: PMC9484572 DOI: 10.2147/oarrr.s285409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/06/2022] [Indexed: 11/28/2022] Open
Abstract
Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease with distinct pathological hallmarks (ie, inflammation, vasculopathy, fibrosis) that may predominate at different stages in the disease course with varying severity. Initial efforts to classify patients with SSc identified a subset of patients with very early SSc. These patients possessed signs of SSc (eg, Raynaud phenomenon, SSc specific autoantibodies and/or nailfold capillary abnormalities) without fulfilling complete SSc classification criteria. Recognizing the inherent value in early diagnosis and intervention in SSc, researchers have endeavored to identify risk factors for progression from very early SSc to definite SSc. The present review summarizes the clinical phenotype of patients with very early and early SSc. Through a scoping review of recent literature, this review also describes risk factors for progression to definite SSc with a focus on the specific clinical features that arise early in the SSc disease course (eg, diffuse cutaneous sclerosis, interstitial lung disease, esophageal dysfunction, renal crisis, cardiac involvement). In addition to clinical risk factors, this review provides evidence for how biological data (ie, serological, genomic, proteomic profiles, skin bioengineering methods) can be integrated into risk assessment models in the future. Furthering our understanding of biological features of very early SSc will undoubtedly provide novel insights into SSc pathogenesis and may illuminate new therapeutic targets to prevent progression of SSc.
Collapse
Affiliation(s)
- Chiara Bellocchi
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of Milan, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Augustine Chung
- Division of Pulmonary and Critical Care, Department of Medicine, University of California, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Elizabeth R Volkmann
- Division of Rheumatology, Department of Medicine, University of California, David Geffen School of Medicine, Los Angeles, CA, USA
| |
Collapse
|
|
30
|
Hernández-Rodríguez JC, Sendín-Martín M, Durán-Romero AJ, Ortiz Álvarez J, Conejo-Mir J, Pereyra-Rodríguez JJ. Systemic sclerosis mortality trends in Spain from 1980 to 2019: age-period-cohort and Joinpoint analysis. Clin Exp Dermatol 2022; 47:1943-1950. [PMID: 35875897 DOI: 10.1111/ced.15342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Systemic sclerosis (SSc) is an autoimmune chronic rheumatic disease with notable mortality that continues to be a challenge for clinicians today. OBJECTIVE To assess changes in mortality trends in the Spanish SSc population between 1980 and 2019, considering the independent effect of sex, age, period and birth cohort. PATIENTS AND METHODS SSc death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for the overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. Similarly, an age-period-cohort (APC) and potential years of life lost (PYLL) analysis were performed to know the burden of SSc. RESULTS Age-standardized mortality rates due to SSc increased from 1.87 (95% CI: 1.00; 3.02) per 1,000,000 inhabitants between 1980 and 1984, to 2.47 (95% CI: 1.74; 3.02) per 1,000,000 inhabitants between 2015 and 2019. The relative risk of mortality fell in cohorts born after 1990 in all groups. The PYLL rates registered a gradual rise in both sexes. CONCLUSIONS Mortality due to SSc in Spain Spain experienced a rise in overall mortality trend during the 39 years of study evaluated, although the male group showed a progressive drop.
Collapse
Affiliation(s)
| | | | | | - Juan Ortiz Álvarez
- Department of Dermatology. Virgen del Rocío University Hospital, Seville, Spain
| | - Julián Conejo-Mir
- Department of Dermatology. Virgen del Rocío University Hospital, Seville, Spain.,Medicine Department. Universidad de Sevilla, Seville, Spain
| | - José-Juan Pereyra-Rodríguez
- Department of Dermatology. Virgen del Rocío University Hospital, Seville, Spain.,Medicine Department. Universidad de Sevilla, Seville, Spain
| |
Collapse
|
|
31
|
Kidney Involvement in Systemic Sclerosis. J Pers Med 2022; 12:jpm12071123. [PMID: 35887620 PMCID: PMC9324204 DOI: 10.3390/jpm12071123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged.
Collapse
|
|
32
|
Suzuki E, Oda R, Kanno T, Kimura S, Saito Y, Kanbayashi H, Matsuda S, Migita K. Pure White Cell Aplasia Complicated by Systemic Sclerosis with Accompanying Scleroderma Renal Crisis. Intern Med 2022; 61:1907-1912. [PMID: 34803102 PMCID: PMC9259819 DOI: 10.2169/internalmedicine.8436-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Pure white cell aplasia (PWCA) is a rare neutropenic disorder caused by absence of neutrophil-lineage cells. A 49-year-old man was diagnosed with scleroderma renal crisis 2 months prior to admission to Ohta-Nishinouchi Hospital after experiencing a fever and abdominal pain. Blood tests revealed severe neutropenia, and bone marrow aspirate showed the absence of neutrophil-lineage cells. He was diagnosed with PWCA. Steroids alone were not effective, but adding cyclosporine A and high-dose immunoglobulin recovered his neutropenia and improved his condition. Cyclosporine A and high-dose immunoglobulin are thus considered effective for treating PWCA in autoimmune diseases.
Collapse
Affiliation(s)
- Eiji Suzuki
- Department of Rheumatology, Ohta-Nishinouchi Hospital, Japan
| | - Ryoma Oda
- Department of Rheumatology, Ohta-Nishinouchi Hospital, Japan
| | - Takashi Kanno
- Department of Rheumatology, Ohta-Nishinouchi Hospital, Japan
| | - Satoru Kimura
- Department of Hematology, Ohta-Nishinouchi Hospital, Japan
| | - Yurie Saito
- Department of Hematology, Ohta-Nishinouchi Hospital, Japan
| | | | - Shin Matsuda
- Department of Hematology, Ohta-Nishinouchi Hospital, Japan
| | - Kiyoshi Migita
- Department of Rheumatology, Fukushima Medical University School of Medicine, Japan
| |
Collapse
|
|
33
|
Gandhi R, Das A, Gonzalez D, Murthy V. Renal Crisis as the Initial Manifestation of Scleroderma. Cureus 2022; 14:e25856. [PMID: 35832752 PMCID: PMC9273168 DOI: 10.7759/cureus.25856] [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: 06/11/2022] [Indexed: 11/18/2022] Open
Abstract
We report the case of a young Hispanic woman who was originally admitted to the emergency department following hypertensive urgency and right-sided blurry vision. The patient did not carry a diagnosis of scleroderma at the time of the visit. However, upon further evaluation, the patient was found to have a scleroderma renal crisis. An angiotensin-converting enzyme (ACE) inhibitor was initiated promptly with subsequent normalization of the blood pressure and creatinine level. Scleroderma renal crisis is a rare, highly feared complication of scleroderma that if left untreated can be life-threatening. Therefore, it is important to identify this condition early and initiate therapy without delay.
Collapse
|
|
34
|
Van Why SK, Pan CG. Primary Causes of Hypertensive Crisis. Crit Care Clin 2022; 38:375-391. [DOI: 10.1016/j.ccc.2021.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
35
|
Palumbo P, Ruscitti P, Cannizzaro E, Berardicurti O, Conforti A, Di Cesare A, Di Cola I, Giacomelli R, Splendiani A, Barile A, Masciocchi C, Cipriani P, Di Cesare E. Unenhanced Cardiac Magnetic Resonance may improve detection and prognostication of an occult heart involvement in asymptomatic patients with systemic sclerosis. Sci Rep 2022; 12:5125. [PMID: 35332224 PMCID: PMC8948177 DOI: 10.1038/s41598-022-09064-5] [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] [Received: 09/18/2021] [Accepted: 03/11/2022] [Indexed: 11/09/2022] Open
Abstract
Systemic sclerosis (SSc) is an uncommon autoimmune disease. Aim of the study was to detect the occult cardiac involvement in asymptomatic SSc patients of recent onset (indicative of a more aggressive disease) with unenhanced Cardiac Magnetic Resonance (CMR). Our historical prospective study included naïve SSc patients of recent onset. Modified Rodnan Skin Score (mRSS) and Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI) were calculated. Cardiac volumes and global myocardial strain were assessed and also compared with healthy group values. Pericardial involvement was further recorded. Thirty-one patients met inclusion criteria (54 ± 12 years; 1 M). Mean duration of disease was 6.8 years. All patients showed preserved systolic function. Higher incidence of pericardial involvement was founded in patients with disease accrual damage (OR: 9.6, p-value 0.01). Radial and longitudinal strain values resulted significantly different between healthy and SSc patients. GRS and GLS showed an independent predictive validity on damage accrual (HR: 1.22 and 1.47, respectively). Best C-index for disease progression was reached when strain values and pericardial evaluation were added to conventional risk factors (0.97, p-value: 0.0001). Strain analysis by CMR-TT may show a high capability both in identifying early cardiac involvement and stratifying its clinical aggressiveness, regardless of the standard damage indices and CMR contrast-dependent biomarker.
Collapse
Affiliation(s)
- Pierpaolo Palumbo
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, Via Saragat -località Campo di Pile, 67100, L'Aquila, Italy. .,SIRM Foundation, Italian Society of Medical and Interventional Radiology (SIRM), 20122, Milan, Italy.
| | - Piero Ruscitti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Ester Cannizzaro
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, Via Saragat -località Campo di Pile, 67100, L'Aquila, Italy
| | - Onorina Berardicurti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Alessandro Conforti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Annamaria Di Cesare
- Ospedale "Infermi" di Rimini, Viale Luigi Settembrini, 2, 47923, Rimini, Italy
| | - Ilenia Di Cola
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Roberto Giacomelli
- Rome Biomedical Campus University, via Álvaro del Portillo 200, 00128, Roma, Italy
| | - Alessandra Splendiani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Antonio Barile
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Carlo Masciocchi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Paola Cipriani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Ernesto Di Cesare
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazzale Salvatore Tommasi 1, 67100, L'Aquila, Italy
| |
Collapse
|
|
36
|
Uddin M, Mir T, Surapaneni S, Mehar A, Dar T, Changal K, Ullah W, Lohia P, Bhat Z, Sheikh M, Burket M. Scleroderma hypertensive renal crisis among systemic sclerosis patients: A national emergency department database study. Am J Emerg Med 2022; 53:228-235. [DOI: 10.1016/j.ajem.2022.01.020] [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] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 11/17/2022] Open
|
|
37
|
Kong W, Wang Y, Wang H, Zhou Q, Chen J, Han F. Systemic sclerosis complicated with renal thrombotic microangiopathy: a case report and literature review. BMC Nephrol 2022; 23:22. [PMID: 35012481 PMCID: PMC8751341 DOI: 10.1186/s12882-021-02639-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 12/15/2021] [Indexed: 11/20/2022] Open
Abstract
Background Systemic sclerosis (SSc) may overlap with other connective tissue diseases, which is named overlap syndrome. Scleroderma renal crisis (SRC) is a rare but severe complication of SSc. SSc related thrombotic microangiopathy (SSc-TMA) is an infrequent pathology type of SRC, while SSc-TMA accompanied by overlap syndrome is very rare. Case presentation This study reported a case of acute kidney injury (AKI) accompanied with overlap syndrome of SSc, systemic lupus erythematosus (SLE) and polymyositis (PM). The renal pathology supported the diagnosis of SSc-TMA but not SLE or PM-related renal injury, characterized by renal arteriolar thrombosis, endothelial cells edema, little cast in tubules and mild immune complex deposition. The primary TMA related factors (ADAMTS13 and complement H factor) were normal. Thus, this case was diagnosed as secondary TMA associated with SSc. The patient was treated with renin angiotensin system inhibitors, sildenafil, supportive plasma exchange/dialysis, and rituximab combined with glucocorticoids. After 2 months of peritoneal dialysis treatment, her renal function recovered and dialysis was stopped. Conclusion This study presented a case of SSc-TMA with overlap syndrome. Rituximab can be used as a treatment option in patients with high SRC risk or already manifesting SRC.
Collapse
Affiliation(s)
- Weiwei Kong
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
| | - Yaomin Wang
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
| | - Huiping Wang
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
| | - Qin Zhou
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
| | - Fei Han
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China.
| |
Collapse
|
|
38
|
Skoumalová A, Horák P, Heřmanová Z, Videman J, Smržová A, Palla V. Early diagnosis of systemic scleroderma. VNITRNI LEKARSTVI 2022; 68:285-289. [PMID: 36283818 DOI: 10.36290/vnl.2022.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Systemic scleroderma (SSc) is a systemic immune-mediated connective tissue disease characterized by fibroproductive changes in connective tissue and microvascular disorders. The disease affects the skin, musculoskeletal system and internal organs. It is a disease with a significant rate of morbidity and mortality, significantly worsening the quality of life of patients. Early initiation of therapy is necessary to prevent disease progression. This review article discusses the current possibilities of early diagnosis of systemic scleroderma.
Collapse
|
|
39
|
Catar R, Herse-Naether M, Zhu N, Wagner P, Wischnewski O, Kusch A, Kamhieh-Milz J, Eisenreich A, Rauch U, Hegner B, Heidecke H, Kill A, Riemekasten G, Kleinau G, Scheerer P, Dragun D, Philippe A. Autoantibodies Targeting AT 1- and ET A-Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor. Int J Mol Sci 2021; 23:244. [PMID: 35008670 PMCID: PMC8745726 DOI: 10.3390/ijms23010244] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 12/20/2022] Open
Abstract
Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT1R) and endothelin-1 type A receptors (ETAR) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT1R or ETAR receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients' autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc.
Collapse
Affiliation(s)
- Rusan Catar
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Melanie Herse-Naether
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Nan Zhu
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
| | - Philine Wagner
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Oskar Wischnewski
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Angelika Kusch
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Berlin Institute of Health, Charité—Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, 10117 Berlin, Germany
| | - Julian Kamhieh-Milz
- Department of Transfusion Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany;
| | - Andreas Eisenreich
- Department of Cardiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (A.E.); (U.R.)
| | - Ursula Rauch
- Department of Cardiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (A.E.); (U.R.)
| | - Björn Hegner
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Vitanas Klinik für Geriatrie, 13435 Berlin, Germany
| | | | - Angela Kill
- Deutsches Rheuma-Forschungszentrum (DRFZ), A. Leibniz Institute, 10117 Berlin, Germany; (A.K.); (G.R.)
- Department of Rheumatology and Clinical Immunology, CCM, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Gabriela Riemekasten
- Deutsches Rheuma-Forschungszentrum (DRFZ), A. Leibniz Institute, 10117 Berlin, Germany; (A.K.); (G.R.)
- Department of Rheumatology and Clinical Immunology, CCM, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Priority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), 23845 Borstel, Germany
| | - Gunnar Kleinau
- Group Protein X-ray Crystallography and Signal Transduction, Institute of Medical Physics and Biophysics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (G.K.); (P.S.)
| | - Patrick Scheerer
- Group Protein X-ray Crystallography and Signal Transduction, Institute of Medical Physics and Biophysics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (G.K.); (P.S.)
- DZHK (Deutsches Zentrum für Herz-Kreislauf Forschung), Partner Site Berlin, 13353 Berlin, Germany
| | - Duska Dragun
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Berlin Institute of Health, Charité—Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, 10117 Berlin, Germany
| | - Aurelie Philippe
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.H.-N.); (N.Z.); (P.W.); (O.W.); (A.K.); (B.H.)
- Center for Cardiovascular Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Berlin Institute of Health, Charité—Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, 10117 Berlin, Germany
| |
Collapse
|
|
40
|
Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review. J Immunol Res 2021; 2021:9782994. [PMID: 34881335 PMCID: PMC8648450 DOI: 10.1155/2021/9782994] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/29/2021] [Indexed: 01/11/2023] Open
Abstract
Background Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. Aim This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. Methods and Results A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. Conclusions Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.
Collapse
|
|
41
|
Hughes M, Kahaleh B, Denton CP, Mason JC, Matucci-Cerinic M. ANCA in systemic sclerosis, when vasculitis overlaps with vasculopathy: a devastating combination of pathologies. Rheumatology (Oxford) 2021; 60:5509-5516. [PMID: 33744916 DOI: 10.1093/rheumatology/keab278] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/24/2021] [Accepted: 03/12/2021] [Indexed: 12/15/2022] Open
Abstract
In patients with SSc, the coexistence of ANCA-associated vasculitis (SSc-AAV) has been reported to be associated with a severe disease course, including significant pulmonary and renal involvement. The presence of ANCA is not uncommon in patients with SSc, and therefore clinicians must maintain a high index of clinical suspicion about SSc-AAV. p-ANCA and anti-myeloperoxidase antibodies are the most common antibodies observed. Patients typically present with clinical features of microscopic polyangiitis or renal-limited vasculitis. There are multiple areas of potential interaction in the pathogenesis of SSc and AAV, which can exacerbate/compound vascular disease. In addition, similar patterns of major internal organ involvement (e.g. lung and kidneys) are seen in both conditions. We highlight a diagnostic approach to SSc-AAV and the paucity of data to inform management. As such, SSc-AAV is typically treated as per isolated AAV, which can potentially be hazardous in patients with SSc (e.g. due to the association between high-dose steroid and scleroderma renal crisis). We propose that this rare clinical entity warrants rigorous investigation, including definition of a therapeutic strategy to ameliorate the potentially devastating combination of pathologies in SSc-AAV.
Collapse
Affiliation(s)
- Michael Hughes
- Department of Rheumatology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Bashar Kahaleh
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA
| | | | - Justin C Mason
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
| |
Collapse
|
|
42
|
Martis N, Jamme M, Bagnis-Isnard C, Pouteil-Noble C, Presne C, Vigneau C, Grangé S, Burtey S, Coindre JP, Wynckel A, Hamidou MA, Kanouni T, Azoulay E, Hié M, Chauveau D, Veyradier A, Rondeau E, Coppo P. Systemic autoimmune disorders associated with thrombotic microangiopathy: A cross-sectional analysis from the French National TMA registry: Systemic autoimmune disease-associated TMA. Eur J Intern Med 2021; 93:78-86. [PMID: 34175183 DOI: 10.1016/j.ejim.2021.05.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/16/2021] [Accepted: 05/28/2021] [Indexed: 12/30/2022]
Abstract
CONTEXT The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. OBJECTIVES To provide a demographic, clinical and therapeutic picture of SAID-TMA. METHODS A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. RESULTS Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjögren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p <0.0005). Two patients died. Thirty patients responded to immunosuppressive treatment and complete remission was achieved in 25 cases. By contrast, therapeutic plasma exchange (TPE) did not have an early effect on TMA features at Day-7 nor Day-15 (p >0.05). CONCLUSION The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. KEY MESSAGES.
Collapse
Affiliation(s)
- Nihal Martis
- Internal Medicine Department, University Hospital of Nice; Côte d'Azur University, Nice, France; French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France.
| | - Matthieu Jamme
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, C.H. Intercommunal Poissy/Saint-Germain-en-Laye, Poissy, France
| | | | - Claire Pouteil-Noble
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Édouard Herriot Hospital, Lyon, France
| | - Claire Presne
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Hôpital Sud, Amiens, France
| | - Cécile Vigneau
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; University of Rennes, University Hospital of Rennes - Inserm, EHESP, Institut de recherche en santé, Environnement et Travail - UMR_S 1085, F-35000 Rennes, France
| | - Steven Grangé
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Intensive Care Unit, C.H.U Rouen, Rouen, France
| | - Stéphane Burtey
- Nephrology Department, C.H.U. de la Conception, Marseille, France
| | | | - Alain Wynckel
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Hôpital Maison Blanche, Reims Cedex, France
| | - Mohamed A Hamidou
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Internal Medicine Department, Hôtel Dieu Hospital, Nantes, France
| | - Tarik Kanouni
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Therapeutic Apheresis Department, C.H.U de Montpellier, Montpellier, France
| | - Elie Azoulay
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Medical Intensive Care Unit, Saint-Louis Hospital, Paris, France
| | - Miguel Hié
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Internal Medicine Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Dominique Chauveau
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology and Kidney transplant Unit, Rangueil Hospital, Toulouse, France
| | - Agnès Veyradier
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Haemostasis Department, Lariboisière Hospital, Paris, France
| | - Eric Rondeau
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology and Kidney transplant Unit, Tenon Hospital, Paris, France
| | - Paul Coppo
- French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Haematology Department, Saint-Antoine Hospital, Paris, France; Sorbonne University, Paris, France.
| |
Collapse
|
|
43
|
Simon M, Lücht C, Hosp I, Zhao H, Wu D, Heidecke H, Witowski J, Budde K, Riemekasten G, Catar R. Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells. Int J Mol Sci 2021; 22:11793. [PMID: 34769227 PMCID: PMC8584031 DOI: 10.3390/ijms222111793] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/19/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). METHODS Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. RESULTS Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. CONCLUSIONS Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC.
Collapse
Affiliation(s)
- Michèle Simon
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | - Christian Lücht
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | - Isa Hosp
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | - Hongfan Zhao
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | - Dashan Wu
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | | | - Janusz Witowski
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
- Department of Pathophysiology, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Klemens Budde
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| | - Gabriela Riemekasten
- Clinic for Rheumatology and Clinical Immunology, Universitätsklinikum Schleswig-Holstein, 23538 Lübeck, Germany;
| | - Rusan Catar
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; (M.S.); (C.L.); (I.H.); (H.Z.); (D.W.); (J.W.); (K.B.)
| |
Collapse
|
|
44
|
Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection. Transplant Direct 2021; 7:e768. [PMID: 34557585 PMCID: PMC8454907 DOI: 10.1097/txd.0000000000001215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 07/02/2021] [Indexed: 01/20/2023] Open
Abstract
Supplemental Digital Content is available in the text. Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR.
Collapse
|
|
45
|
Abbas F, El Kossi M, Shaheen IS, Sharma A, Halawa A. Journey of a patient with scleroderma from renal failure up to kidney transplantation. World J Transplant 2021; 11:372-387. [PMID: 34631469 PMCID: PMC8465513 DOI: 10.5500/wjt.v11.i9.372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/10/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.
Collapse
Affiliation(s)
- Fedaey Abbas
- Department of Nephrology, Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Doncaster Renal Unit, Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Ihab Sakr Shaheen
- Department of Paediatric Nephrology, St James’s University Hospital, Glasgow G51 4TF, United Kingdom
| | - Ajay Sharma
- Department of Transplant Surgery, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Department of Transplant Surgery, Sheffield Teaching Hospital, Sheffield S5 7AU, United Kingdom
| |
Collapse
|
|
46
|
Beghé B, Cerri S, Fabbri LM, Marchioni A. COPD, Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors. Int J Mol Sci 2021; 22:ijms22179292. [PMID: 34502194 PMCID: PMC8430914 DOI: 10.3390/ijms22179292] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 01/19/2023] Open
Abstract
Aging and smoking are associated with the progressive development of three main pulmonary diseases: chronic obstructive pulmonary disease (COPD), interstitial lung abnormalities (ILAs), and idiopathic pulmonary fibrosis (IPF). All three manifest mainly after the age of 60 years, but with different natural histories and prevalence: COPD prevalence increases with age to >40%, ILA prevalence is 8%, and IPF, a rare disease, is 0.0005–0.002%. While COPD and ILAs may be associated with gradual progression and mortality, the natural history of IPF remains obscure, with a worse prognosis and life expectancy of 2–5 years from diagnosis. Acute exacerbations are significant events in both COPD and IPF, with a much worse prognosis in IPF. This perspective discusses the paradox of the striking pathological and pathophysiologic responses on the background of the same main risk factors, aging and smoking, suggesting two distinct pathophysiologic processes for COPD and ILAs on one side and IPF on the other side. Pathologically, COPD is characterized by small airways fibrosis and remodeling, with the destruction of the lung parenchyma. By contrast, IPF almost exclusively affects the lung parenchyma and interstitium. ILAs are a heterogenous group of diseases, a minority of which present with the alveolar and interstitial abnormalities of interstitial lung disease.
Collapse
Affiliation(s)
- Bianca Beghé
- Respiratory Diseases Unit, University Hospital of Modena, 41124 Modena, Italy; (S.C.); (A.M.)
- Correspondence:
| | - Stefania Cerri
- Respiratory Diseases Unit, University Hospital of Modena, 41124 Modena, Italy; (S.C.); (A.M.)
| | - Leonardo M. Fabbri
- Department of Translational Medicine and Romagna, University of Ferrara, 44121 Ferrara, Italy;
| | - Alessandro Marchioni
- Respiratory Diseases Unit, University Hospital of Modena, 41124 Modena, Italy; (S.C.); (A.M.)
| |
Collapse
|
|
47
|
Htet Z, Karim M. Thrombotic microangiopathy with renal injury: an approach for the general physician. J R Coll Physicians Edinb 2021; 50:25-31. [PMID: 32539032 DOI: 10.4997/jrcpe.2020.107] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Thrombotic microangiopathy with renal dysfunction is a haematological and renal emergency warranting urgent diagnosis and intervention. As the potential underlying causes may be complex, assessment and management can be challenging for treating clinicians, and a timely and collaborative approach between general physicians, haematologists and nephrologists may be extremely helpful in order to optimise clinical outcomes. This paper will aim to build an understanding of different potential presentations of thrombotic microangiopathies and provide a practical framework for diagnosis and management, using a case-based discussion format, for acute and general physicians. Some aspects of subsequent specialist management are also discussed.
Collapse
Affiliation(s)
- Zay Htet
- Department of Renal Medicine, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK,
| | - Mahzuz Karim
- Department of Renal Medicine, Norfolk and Norwich University Hospital, Norwich, UK
| |
Collapse
|
|
48
|
Odler B, Hebesberger C, Hoeflechner L, Pregartner G, Gressenberger P, Jud P, Zenz S, Eller K, Rosenkranz AR, Moazedi‐Fuerst F. Effect of short-interval rituximab and high-dose corticosteroids on kidney function in systemic sclerosis: Long-term experience of a single centre. Int J Clin Pract 2021; 75:e14069. [PMID: 33540483 PMCID: PMC8243981 DOI: 10.1111/ijcp.14069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 02/01/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Scleroderma renal crisis (SRC) is a rare but one of the most recognised complications of systemic sclerosis (SSc). Corticosteroid (CS) use has been considered as a major risk factor for SRC. Several studies reported the efficacy of rituximab (RTX) with an acceptable safety profile in SSc. However, data on the long-term effect of high-dose CS concomitant to RTX on kidney function are lacking. METHODS We retrospectively analysed SSc patients (n = 35) treated with a lower dosage and short-interval RTX and concomitant high-dose CS at the Department of Internal Medicine at the Medical University of Graz between 2010 and 2019. The kidney function was assessed using the estimated glomerular filtration rate (eGFR) at every RTX admission. The annual decline of kidney function was evaluated by linear mixed model analysis. RESULTS At the RTX initiation, one patient had a decreased kidney function indicated by eGFR < 60 mL/min/1.73 m2 (median: 96 mL/min/1.73 m2 ; interquartile range (IQR): 43-136). Patients received RTX and complementary high-dose CS for a median follow-up time of 3.4 years (range 0.6-9.5). A linear mixed model analysis with the patient as random effect and time from first RTX as fixed effect estimated an annual decline of 1.98 mL/min/1.73 m2 of the eGFR (95% confidence interval: [-2.24, -1.72]; P <.001). During the follow-up period, no patient experienced SRC or a significant drop in kidney function. CONCLUSIONS A regular, high-dose CS given contemporary to RTX seems to be a safe option for kidney function in patients with SSc. Our findings provide additional knowledge in risk evaluation and planning of individualised therapies or designing clinical studies using RTX.
Collapse
Affiliation(s)
- Balazs Odler
- Division of NephrologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Carina Hebesberger
- Division of NephrologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Lukas Hoeflechner
- Division of NephrologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics and DocumentationMedical University of GrazGrazAustria
| | - Paul Gressenberger
- Division of AngiologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Philipp Jud
- Division of AngiologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Sabine Zenz
- Division of Rheumatology and ImmunologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Kathrin Eller
- Division of NephrologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | | | - Florentine Moazedi‐Fuerst
- Division of Rheumatology and ImmunologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| |
Collapse
|
|
49
|
Wu R, Su J, Zou YR, Zhu J. ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review. Eur J Med Res 2021; 26:30. [PMID: 33789719 PMCID: PMC8011393 DOI: 10.1186/s40001-021-00500-2] [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: 10/21/2020] [Accepted: 03/15/2021] [Indexed: 11/10/2022] Open
Abstract
Background Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV. Case presentation Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge. Conclusions AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.
Collapse
Affiliation(s)
- Rui Wu
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 The First Ring Road West 2, Chengdu, 610072, China.,Department of Rheumatology and Immunology, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, China
| | - Jiang Su
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 The First Ring Road West 2, Chengdu, 610072, China.,Department of Rheumatology and Immunology, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, China
| | - Yu-Rong Zou
- Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Jing Zhu
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 The First Ring Road West 2, Chengdu, 610072, China. .,Department of Rheumatology and Immunology, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, China.
| |
Collapse
|
|
50
|
Gouin A, Ribes D, Colombat M, Chauveau D, Prevot G, Lairez O, Pugnet G, Fremeaux-Bacchi V, Huart A, Belliere J, Faguer S. Role of C5 inhibition in Idiopathic Inflammatory Myopathies and Scleroderma Renal Crisis-Induced Thrombotic Microangiopathies. Kidney Int Rep 2021; 6:1015-1021. [PMID: 33912751 PMCID: PMC8071645 DOI: 10.1016/j.ekir.2021.01.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction Connective tissue diseases, including systemic sclerosis and idiopathic inflammatory myopathies (IIMs), are a very rare cause of thrombotic microangiopathies (TMAs). Whether dysregulation of the complement pathways underlies these secondary forms of TMA and may be targeted by complement blocking agents remains elusive. Methods Kidney pathology and outcomes of 18 critically ill patients with TMA related to inflammatory myopathy flare-up (IIM, n=7) or scleroderma renal crisis (SRC, n=11; biopsy n=9) are assessed. Results IIM-TMA is characterized by acute thrombotic lesions only, whereas SRC-TMA patients also harbored chronic vascular lesions and more interstitial fibrosis. C5b9 deposits, a marker of complement component 5 (C5) cleavage, were observed in the 2 subgroups at the junction of media and intima of arterioles, colocalizing with subendothelial edema. Thus, kidney biopsy distinguished between acute and chronic renal phenotypes that may help to individualize treatment. Treatment of IIM-TMA patients with combined full-code organ support, corticosteroids, B-cell depletion, and complement C5 blocking led to 1-year survival of 72%, compared with 19% in historical cohorts. Treatment of SRC-TMA was more heterogenous and relied on conversion enzyme inhibitor only or with eculizumab (n=6) and immunosuppressor (n=5). One-year survival of SRC-TMA patients was 52%, a result similar to historical cohorts. Eculizumab was followed by a rapid dramatic improvement of TMA in all the treated patients. Conclusion C5 blocking may reverse hematologic abnormalities in IIM- and SRC-TMA, and adding an early and aggressive immunosuppressive regimen may improve the survival of IIM-TMA. Underlying chronic vascular and interstitial lesions mitigate renal response in SRC-TMA.
Collapse
Affiliation(s)
- Anna Gouin
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| | - David Ribes
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| | - Magali Colombat
- Service d'anatomopathologie, Institut Universitaire du Cancer de Toulouse - Oncopole, Centre Hospitalier Universitaire, Toulouse, France
| | - Dominique Chauveau
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| | - Gregoire Prevot
- Service de Pneumologie, Centre Hospitalier Universitaire, Toulouse, France
| | - Olivier Lairez
- Fédération de Cardiologie, Centre Hospitalier Universitaire, Toulouse, France
| | - Gregory Pugnet
- Service de Médecine Interne, Centre Hospitalier Universitaire, Toulouse, France
| | | | - Antoine Huart
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| | - Julie Belliere
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| | - Stanislas Faguer
- Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France
| |
Collapse
|