|
1
|
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
|
|
2
|
Li X, Zhang H, Zhang X, Wang G, Zhao X, Zhang J. A comparative study of different types of connective tissue-associated interstitial lung disease. BMC Med Imaging 2025; 25:109. [PMID: 40197179 PMCID: PMC11977872 DOI: 10.1186/s12880-025-01655-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 03/31/2025] [Indexed: 04/10/2025] Open
Abstract
INTRODUCTION Interstitial lung disease (ILD) is an important pulmonary complication of connective tissue disease (CTD). This study aimed to analyze high-resolution computed tomography (HRCT) manifestations of different connective tissue-associated interstitial lung diseases (CTD-ILDs) to improve diagnostic accuracy. METHOD This study retrospectively included 99 patients diagnosed with CTD-ILD between September 2017 and July 2024. Visual assessment and quantitative CT analysis were used to evaluate HRCT manifestations. RESULTS The age of the rheumatoid arthritis (RA) group was significantly greater than that of the polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc) groups (p = 0.025 and p = 0.02), with a mean age of 64.4 ± 10 years. The most common HRCT pattern of CTD-ILD was nonspecific interstitial pneumonia (NSIP) (p = 0.008); the adjusted residual > 1.96, usual interstitial pneumonia (UIP) was most frequently observed in the RA group, organizing pneumonia (OP) was most commonly observed in the PM/DM group, and lymphocytic interstitial pneumonia (LIP) was observed only in the primary Sjögren's syndrome (pSjS) group. The CTD-ILD groups exhibited significant differences in bronchiectasis (χ2 = 11.256, p = 0.0022), esophageal dilatation (χ2 = 33.923, p < 0.001), mediastinal lymph node enlargement (χ2 = 10.103, p = 0.041), and thin-walled cysts (χ2 = 14.081, p = 0.006). Adjusted residual > 1.96, esophageal dilatation was commonly observed in the SSc group; bronchiectasis was more common in the RA group; mediastinal lymph node was more common in the pSjS group. Statistically significant differences in the predominance of different CTD-ILDs (χ2 = 20.814, p = 0.0046). The PM/DM group exhibited significant consolidation and reticulation. The extensive honeycombing was present in the RA-ILD group (p = 0.044). Based on logistic binary regression analysis, bronchial dilatation (odds ratio: 4.506, p = 0.005) and extensive honeycombing (odds ratio: 1.282, p = 0.021) were significant predictors of RA-ILD, while lymph node enlargement (odds ratio: 3.314, p = 0.039) and thin-walled cysts (odds ratio: 6.278, p = 0.001) were predictors of pSjS-ILD. CONCLUSION Different types of CTD-ILD have characteristic HRCT manifestations. CLINICAL TRIAL NUMBER As this study involved standard clinical procedures and assessments without an experimental treatment protocol, it did not require registration with a public clinical trials registry.
Collapse
Affiliation(s)
- Xinyi Li
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China
| | - Hongmei Zhang
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China
| | - Xiaoyue Zhang
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China
| | - Guokun Wang
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China
| | - Xue Zhao
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China
| | - Jinling Zhang
- Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 15000, China.
| |
Collapse
|
|
3
|
Barbosa Franco Zörrer LA, Yugi de Souza Terui L, Fanini Balena R, Woidello Miyazima AL, Miyazima R. Diffuse Cutaneous Systemic Sclerosis With Normotensive Scleroderma Renal Crisis and Myopericarditis: A Case Report. Cureus 2025; 17:e78858. [PMID: 40084306 PMCID: PMC11906016 DOI: 10.7759/cureus.78858] [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: 02/11/2025] [Indexed: 03/16/2025] Open
Abstract
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis and multi-organ dysfunction, primarily affecting the heart, lungs, and kidneys. Scleroderma renal crisis (SRC) can present as hypertensive or normotensive, with the latter being more challenging to diagnose due to the absence of hypertension at onset. Normotensive SRC carries a worse prognosis, with an increased risk of renal failure and a poor response to treatment. The presence of cardiac complications, such as myopericarditis, further exacerbates the clinical course, creating significant management challenges. Moreover, hypotension in normotensive SRC complicates therapeutic interventions, particularly the use of angiotensin-converting enzyme (ACE) inhibitors. This case report highlights a patient with diffuse cutaneous systemic sclerosis (dcSSc) who presented with normotensive SRC complicated by myopericarditis, resulting in acute renal and heart failure. It underscores the need for early recognition of this rare form of renal crisis, especially when accompanied by cardiac complications, given its atypical presentation without significant hypertension at onset. The report emphasizes the critical importance of identifying risk factors and addressing the challenges of managing normotensive SRC to improve patient outcomes.
Collapse
Affiliation(s)
| | | | - Rodrigo Fanini Balena
- Internal Medicine, Clinical Hospital Complex of the Federal University of Paraná, Curitiba, BRA
| | | | - Rafael Miyazima
- Internal Medicine, Clinical Hospital Complex of the Federal University of Paraná, Curitiba, BRA
| |
Collapse
|
|
4
|
Muruganandam M, Akpan EB, McElwee MK, Emil NS, Keller MC, Vangala AS, Dihowm F, Nunez SE, Gibb JI, O'Sullivan FX, Fields RA, Sibbitt WL. Scleroderma Renal Crisis and Musculoskeletal Corticosteroid Injections. J Clin Rheumatol 2025; 31:12-19. [PMID: 39527973 DOI: 10.1097/rhu.0000000000002168] [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: 11/16/2024]
Abstract
BACKGROUND/OBJECTIVE Inflammatory arthritis frequently affects patients with systemic sclerosis (SSc) but musculoskeletal corticosteroid (MSKC) injections are often avoided due to concerns of scleroderma renal crisis (SRC). This study investigated the incidence of SRC following MSKC injections. METHODS In a 136-SSc cohort, 46 subjects underwent a total of 330 MSKC injections each receiving a significant dosage of triamcinolone acetonide (mean, 95.2 ± 44.2 mg per injection session). Data on blood pressure (BP), serum creatinine and glucose, urine protein, and complications were obtained before and after injection from the patients' medical records. RESULTS MSKC and control subjects were similar in age (MSKC: 58.9 ± 12.1 vs. 55.5 ± 14.9 years), female (MSKC: 97.8% [45/46] vs. 89.9% [81/90]), antinuclear antibody (MSKC: 71.7% [33/46] vs. 81.1% [73/90]), anti-centromere antibody (MSKC: 47.8% [22/46] vs. 37.8% [34/90]), anti-topoisomerase antibody (MSKC: 26.1% [12/46] vs. 26.7% [24/90]), and anti-RNA polymerase III antibody (MSKC: 17.4.1% [8/46] vs. 24.4% [22/90]) (all p > 0.05). Pre- and post-MSKC demonstrated nonsignificant changes in systolic BP (pre: 127 ± 22 vs. post: 127 ± 21 mm Hg, p = 1.0), diastolic BP (pre: 71 ± 13 vs. post: 71 ± 11 mm Hg, p = 1.0), creatinine (pre: 0.78 ± 0.56 vs. post: 0.76 ± 0.20 mg/dL, p = 0.64), glucose (pre: 100 ± 21 vs. post: 99 ± 24 mg/dL, p = 0.67), and urine protein-creatinine ratio (pre: 0.14 ± 0.12 vs. post: 0.12 ± 0.11 mg/mg, p = 0.41). One case of SRC with mortality occurred in the controls and none in the MSKC group. No infections, hematologic abnormalities, or tendon rupture were noted. CONCLUSION MSKC injections in established SSc are generally safe with low incidences of SRC and complications. However, it is still prudent to monitor high-risk individuals and recent-onset SSc post-MSKC injection.
Collapse
|
|
5
|
Johnson SR, Bernstein EJ, Bolster MB, Chung JH, Danoff SK, George MD, Khanna D, Guyatt G, Mirza RD, Aggarwal R, Allen A, Assassi S, Buckley L, Chami HA, Corwin DS, Dellaripa PF, Domsic RT, Doyle TJ, Falardeau CM, Frech TM, Gibbons FK, Hinchcliff M, Johnson C, Kanne JP, Kim JS, Lim SY, Matson S, McMahan ZH, Merck SJ, Nesbitt K, Scholand MB, Shapiro L, Sharkey CD, Summer R, Varga J, Warrier A, Agarwal SK, Antin-Ozerkis D, Bemiss B, Chowdhary V, Dematte D'Amico JE, Hallowell R, Hinze AM, Injean PA, Jiwrajka N, Joerns EK, Lee JS, Makol A, McDermott GC, Natalini JG, Oldham JM, Saygin D, Lakin KS, Singh N, Solomon JJ, Sparks JA, Turgunbaev M, Vaseer S, Turner A, Uhl S, Ivlev I. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases. Arthritis Care Res (Hoboken) 2024; 76:1051-1069. [PMID: 38973731 DOI: 10.1002/acr.25348] [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: 08/21/2023] [Revised: 01/18/2024] [Accepted: 04/09/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVE We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.
Collapse
Affiliation(s)
- Sindhu R Johnson
- University of Toronto, Schroeder Arthritis Institute, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Elana J Bernstein
- Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City
| | | | | | - Sonye K Danoff
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | | | | | | | | | | | - Hassan A Chami
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | | | | | - Tracy M Frech
- Vanderbilt University Medical Center, Nashville, Tennessee
| | | | | | | | - Jeffrey P Kanne
- University of Wisconsin School of Medicine and Public Health, Madison
| | - John S Kim
- University of Virginia School of Medicine, Charlottesville
| | | | - Scott Matson
- University of Kansas Medical Center, Kansas City
| | | | | | | | | | | | | | - Ross Summer
- Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Didem Saygin
- University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | - Stacey Uhl
- Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania
| | - Ilya Ivlev
- Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania
| |
Collapse
|
|
6
|
Ahmed AA, Said D, Sami MM. Growth arrest-specific protein 6 as a marker of nephritis in systemic sclerosis and juvenile systemic lupus erythematosus patients. Lupus 2024; 33:910-917. [PMID: 38809681 DOI: 10.1177/09612033241257321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300 mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2 ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.
Collapse
Affiliation(s)
- Alshymaa A Ahmed
- Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Dina Said
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - May M Sami
- Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| |
Collapse
|
|
7
|
Johnson SR, Bernstein EJ, Bolster MB, Chung JH, Danoff SK, George MD, Khanna D, Guyatt G, Mirza RD, Aggarwal R, Allen A, Assassi S, Buckley L, Chami HA, Corwin DS, Dellaripa PF, Domsic RT, Doyle TJ, Falardeau CM, Frech TM, Gibbons FK, Hinchcliff M, Johnson C, Kanne JP, Kim JS, Lim SY, Matson S, McMahan ZH, Merck SJ, Nesbitt K, Scholand MB, Shapiro L, Sharkey CD, Summer R, Varga J, Warrier A, Agarwal SK, Antin-Ozerkis D, Bemiss B, Chowdhary V, Dematte D'Amico JE, Hallowell R, Hinze AM, Injean PA, Jiwrajka N, Joerns EK, Lee JS, Makol A, McDermott GC, Natalini JG, Oldham JM, Saygin D, Lakin KS, Singh N, Solomon JJ, Sparks JA, Turgunbaev M, Vaseer S, Turner A, Uhl S, Ivlev I. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases. Arthritis Rheumatol 2024; 76:1182-1200. [PMID: 38978310 DOI: 10.1002/art.42861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 01/18/2024] [Accepted: 04/09/2024] [Indexed: 07/10/2024]
Abstract
OBJECTIVE We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.
Collapse
Affiliation(s)
- Sindhu R Johnson
- University of Toronto, Schroeder Arthritis Institute, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Elana J Bernstein
- Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City
| | | | | | - Sonye K Danoff
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | | | | | | | | | | | - Hassan A Chami
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | | | | | - Tracy M Frech
- Vanderbilt University Medical Center, Nashville, Tennessee
| | | | | | | | - Jeffrey P Kanne
- University of Wisconsin School of Medicine and Public Health, Madison
| | - John S Kim
- University of Virginia School of Medicine, Charlottesville
| | | | - Scott Matson
- University of Kansas Medical Center, Kansas City
| | | | | | | | | | | | | | - Ross Summer
- Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Didem Saygin
- University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | - Stacey Uhl
- Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania
| | - Ilya Ivlev
- Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania
| |
Collapse
|
|
8
|
Chevalier K, Chassagnon G, Leonard-Louis S, Cohen P, Dunogue B, Regent A, Thoreau B, Mouthon L, Chaigne B. Anti-U1RNP antibodies are associated with a distinct clinical phenotype and a worse survival in patients with systemic sclerosis. J Autoimmun 2024; 146:103220. [PMID: 38642508 DOI: 10.1016/j.jaut.2024.103220] [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: 01/24/2024] [Revised: 03/24/2024] [Accepted: 03/31/2024] [Indexed: 04/22/2024]
Abstract
OBJECTIVES To clarify the impact of anti-U1RNP antibodies on the clinical features and prognosis of patients with SSc. METHODS We conducted a monocentric case-control, retrospective, longitudinal study. For each patient with SSc and anti-U1RNP antibodies (SSc-RNP+), one patient with mixed connective tissue disease (MCTD) and 2 SSc patients without anti-U1RNP antibodies (SSc-RNP-) were matched for age, sex, and date of inclusion. RESULTS Sixty-four SSc-RNP+ patients were compared to 128 SSc-RNP- and 64 MCTD patients. Compared to SSc-RNP-, SSc-RNP+ patients were more often of Afro-Caribbean origin (31.3% vs. 11%, p < 0.01), and more often had an overlap syndrome than SSc-RNP- patients (53.1 % vs. 22.7%, p < 0.0001), overlapping with Sjögren's syndrome (n = 23, 35.9%) and/or systemic lupus erythematosus (n = 19, 29.7%). SSc-RNP+ patients were distinctly different from MCTD patients but less often had joint involvement (p < 0.01). SSc-RNP+ patients more frequently developed interstitial lung disease (ILD) (73.4% vs. 55.5% vs. 31.3%, p < 0.05), pulmonary fibrosis (PF) (60.9% vs. 37.5% vs. 10.9%, p < 0.0001), SSc associated myopathy (29.7% vs. 6.3% vs. 7.8%, p < 0.0001), and kidney involvement (10.9% vs. 2.3% vs. 1.6%, p < 0.05). Over a 200-month follow-up period, SSc-RNP+ patients had worse overall survival (p < 0.05), worse survival without PF occurrence (p < 0.01), ILD or PF progression (p < 0.01 and p < 0.0001). CONCLUSIONS In SSc patients, anti-U1RNP antibodies are associated with a higher incidence of overlap syndrome, a distinct clinical phenotype, and poorer survival compared to SSc-RNP- and MCTD patients. Our study suggests that SSc-RNP+ patients should be separated from MCTD patients and may constitute an enriched population for progressive lung disease.
Collapse
Affiliation(s)
- Kevin Chevalier
- 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, Paris, France
| | - Guillaume Chassagnon
- Department of Radiology, Hôpital Cochin, AP-HP. Centre Université Paris Cité, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France; Université Paris Cité, 85 Boulevard Saint-Germain, 75006, Paris, France
| | - Sarah Leonard-Louis
- Sorbonne Université, INSERM, Department of Neurormyologie and Neuropathology, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
| | - Pascal Cohen
- 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, Paris, France
| | - Bertrand Dunogue
- 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, Paris, France
| | - Alexis Regent
- 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, Paris, France
| | - Benjamin Thoreau
- 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, 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 (AP-HP), France; APHP-CUP, Hôpital Cochin, Université Paris Cité, F-75014, Paris, France.
| |
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
|
Foeldvari I, Torok KS, Antón J, Blakley M, Constantin T, Cutolo M, Denton CP, Fligelstone K, Hinrichs B, Li SC, Maillard S, Marrani E, Moinzadeh P, Orteu CH, Pain CE, Pauling JD, Pilkington C, Rosser F, Smith V, Furst DF. Best clinical practice in the treatment of juvenile systemic sclerosis: expert panel guidance - the result of the International Hamburg Consensus Meeting December 2022. Expert Rev Clin Immunol 2024; 20:387-404. [PMID: 38149621 DOI: 10.1080/1744666x.2023.2298354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/19/2023] [Indexed: 12/28/2023]
Abstract
INTRODUCTION Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed. AREAS COVERED Treatment options were reviewed, and opinions were provided for most facets of jSSc including general management, some of which differs from adult systemic sclerosis, such as the use of corticosteroids, and specific organ involvement, such as skin, musculoskeletal, pulmonary, and gastroenterology. EXPERT OPINION We are suggesting the treat to target strategy to treat early to prevent cumulative disease damage in jSSc. Conclusions are derived from both expert opinion and available literature, which is mostly based on adult systemic sclerosis (aSSc), given shared pathophysiology, extrapolation of results from aSSc studies was judged reasonable.
Collapse
Affiliation(s)
- Ivan Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | - Kathryn S Torok
- University of Pittsburgh and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Jordi Antón
- Department of Pediatric Rheumatology. Hospital Sant Joan de Déu and Universitat de Barcelona, Barcelona, Spain
| | - Michael Blakley
- Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tamás Constantin
- Unit of Pediatric Rheumatology, Tűzoltó Street Department, Pediatric Centre, Semmelweis University, Budapest, Hungary
| | - Maurizio Cutolo
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology-Department of Internal Medicine and Specialties, University of Genoa and IRCCS San Martino Polyclinic Hospital, Genoa, Italy
| | | | - Kim Fligelstone
- Scleroderma & Raynaud's United Kindgom (SRUK) (Research Subcommittee, Patient Research Partner), FESCA, London, UK
| | - Bernd Hinrichs
- Children's pulmonology, Asklepios Klinik Nord - Heidberg, Hamburg, Germany
| | - Suzanne C Li
- Hackensack University Medical Center, Hackensack, NJ, USA
| | | | - Edoardo Marrani
- Pediatric Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy
| | - Pia Moinzadeh
- Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany
| | - Catherine H Orteu
- UCL Institute of Immunity and Transplantation, Royal Free London NHS Foundation Trust, London, UK
| | - Clare E Pain
- Alder Hey Children's Foundation NHS Trust, Liverpool, UK
| | - John D Pauling
- Department of Internal Medicine, Ghent University, Ghent, Belgium
- Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
- Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium and ERN ReCONNET
| | | | - Franziska Rosser
- University of Pittsburgh and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Vanessa Smith
- University of California, Los Angeles, CA, USA
- University of Washington, Seattle, WA, USA
- University of Florence, Florence, Italy
| | - Daniel F Furst
- Division of Rheumatology Fellow, Geffen School of Medicine at the University of California in Los Angeles, Los Angeles, CA, USA
| |
Collapse
|
|
11
|
Mouthon L. [Autologous peripheral stem cell transplantation in systemic sclerosis: An important step forward, but we must temper our enthusiasm!]. Rev Med Interne 2024; 45:100-103. [PMID: 38238136 DOI: 10.1016/j.revmed.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/12/2024]
Abstract
Three prospective randomized studies have demonstrated the efficacy of autologous hematopoietic stem cell (HSC) transplantation in systemic sclerosis (SSc) on survival. These results encourage us to offer this therapy to patients who have a rapidly progressive disease and who have early symptoms but no advanced visceral involvement. HSC autograft can thus be discussed in patients with diffuse cutaneous SSc with a duration of the disease since the first visceral manifestations (cutaneous, cardiac, digestive, pulmonary, or renal) excluding Raynaud's phenomenon of less than 5 years. However, the indications for HSC autograft in SSc validated at European level and in the national diagnostic and care protocol (PNDS) are broader and some of these indications are debatable, in particular in patients with worsening diffuse interstitial lung disease. These indications are discussed in a reasoned way, taking into account the level of evidence and the toxicity of the HSC autograft.
Collapse
Affiliation(s)
- L Mouthon
- Service de médecine interne, centre de référence maladies autoimmunes et autoinflammatoires systémiques rares d'Ile de France, de l'Est et de l'Ouest, hôpital Cochin, Assistance Publique-hôpitaux de Paris (AP-HP), hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, AP-HP-CUP, Hôpital Cochin, 75014 Paris, France.
| |
Collapse
|
|
12
|
Mouthon L. [Autologous peripheral stem cell transplantation in systemic sclerosis: An important step forward, but we must temper our enthusiasm!]. Rev Med Interne 2023:S0248-8663(23)01297-3. [PMID: 38057166 DOI: 10.1016/j.revmed.2023.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2023]
Abstract
Three prospective randomized studies have demonstrated the efficacy of autologous hematopoietic stem cell (HSC) transplantation in systemic sclerosis (SSc) on survival. These results encourage us to offer this therapy to patients who have a rapidly progressive disease and who have early symptoms but no advanced visceral involvement. HSC autograft can thus be discussed in patients with diffuse cutaneous SSc with a duration of the disease since the first visceral manifestations (cutaneous, cardiac, digestive, pulmonary, or renal) excluding Raynaud's phenomenon of less than 5 years. However, the indications for HSC autograft in SSc validated at European level and in the national diagnostic and care protocol (PNDS) are broader and some of these indications are debatable, in particular in patients with worsening diffuse interstitial lung disease. These indications are discussed in a reasoned way, taking into account the level of evidence and the toxicity of the HSC autograft.
Collapse
Affiliation(s)
- L Mouthon
- Service de médecine interne, centre de référence maladies auto-immunes systémiques rares d'Île-de-France, hôpital Cochin, Assistance publique-Hôpitaux de Paris (AP-HP), 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Hôpital Cochin, université Paris Cité, AP-HP - CUP, 75014 Paris, France.
| |
Collapse
|
|
13
|
Strunz PP, Labinsky H, Nagler LK, Portegys J, Froehlich M, Gernert M, Schmalzing M. Case Report: Effectiveness of secukinumab in systemic sclerosis with early skin progress after autologous hematopoietic stem cell transplantation and end-stage kidney disease. Front Immunol 2023; 14:1294496. [PMID: 38045701 PMCID: PMC10693324 DOI: 10.3389/fimmu.2023.1294496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/03/2023] [Indexed: 12/05/2023] Open
Abstract
Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment option in patients with severe forms of systemic sclerosis (SSc) by resetting the immune system. Nevertheless, secondary autoimmune disorders and progressive disease after aHSCT might necessitate renewed immunosuppressive treatments. This is particularly challenging when organ dysfunction, i.e., end-stage kidney failure, is present. In this case report, we present the unique case of a 43-year-old female patient with rapidly progressive diffuse systemic sclerosis who underwent aHSCT despite end-stage renal failure as consequence of SSc-renal crisis. Therefore, conditioning chemotherapy was performed with melphalan instead of cyclophosphamide with no occurrence of severe adverse events during the aplastic period and thereafter. After aHSCT, early disease progression of the skin occurred and was successfully treated with secukinumab. Thereby, to the best of our knowledge, we report the first case of successful aHSCT in a SSc-patient with end-stage kidney failure and also the first successful use of an IL-17 inhibitor to treat early disease progression after aHSCT.
Collapse
Affiliation(s)
- Patrick-Pascal Strunz
- Department of Internal Medicine 2, Rheumatology/Clinical Immunology, University Hospital Würzburg, Würzburg, Germany
| | | | | | | | | | | | | |
Collapse
|
|
14
|
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
|
|
15
|
Barbacki A, Baron M, Wang M, Zhang Y, Stevens W, Sahhar J, Proudman S, Nikpour M, Man A. Damage Trajectories in Systemic Sclerosis Using Group-Based Trajectory Modeling. Arthritis Care Res (Hoboken) 2023; 75:640-647. [PMID: 35226416 DOI: 10.1002/acr.24873] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 02/11/2022] [Accepted: 02/24/2022] [Indexed: 11/12/2022]
Abstract
OBJECTIVE Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive organ damage, which can be measured using the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We aimed to identify whether distinct trajectories of damage accrual exist and to determine which variables are associated with different trajectory groups. METHODS Incident cases of SSc (<2 years) were identified in the Australian Scleroderma Interest Group and Canadian Scleroderma Research Group prospective registries. Group-based trajectory modeling was used to identify SCTC-DI trajectories over the cohort's first 5 annual visits. Baseline variables associated with trajectory membership in a univariate analysis were examined in multivariable models. RESULTS A total of 410 patients were included. Three trajectory groups were identified: low (54.6%), medium (36.2%), and high (10.3%) damage. Patients with faster damage accrual had higher baseline SCTC-DI scores. Older age (odds ratio [OR] 1.57 [95% confidence interval (95% CI) 1.18-2.10]), male sex (OR 2.55 [95% CI 1.10-5.88]), diffuse disease (OR 6.7 [95% CI 2.57-17.48]), tendon friction rubs (OR 5.4 [95% CI 1.86-15.66]), and elevated C-reactive protein level (OR 1.98 [95% CI 1.49-2.63]) increased the odds of being in the high-damage group versus the reference (low damage), whereas White ethnicity (OR 0.31 [95% CI 0.12-0.75]) and anticentromere antibodies (OR 0.24 [95% CI 0.07-0.77]) decreased the odds. CONCLUSION We identified 3 trajectories of damage accrual in a combined incident SSc cohort. Several characteristics increased the odds of belonging to worse trajectories. These findings may be helpful in recognizing patients in whom early aggressive treatment is necessary.
Collapse
Affiliation(s)
- Ariane Barbacki
- Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
| | - Murray Baron
- Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
| | - Mianbo Wang
- Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
| | - Yuqing Zhang
- Massachusetts General Hospital, Harvard Medical School, Boston
| | - Wendy Stevens
- St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | | | - Susanna Proudman
- Royal Adelaide Hospital, North Terrace, Adelaide, South Australia
| | - Mandana Nikpour
- University of Melbourne at St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Ada Man
- University of Manitoba, Winnipeg, Manitoba, Canada
| | | |
Collapse
|
|
16
|
Chew E, Barnado A, Ikizler TA, Zent R, Frech T. Evaluation of hypertension in systemic sclerosis and systemic lupus erythematosus overlap. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2023; 8:14-19. [PMID: 36743818 PMCID: PMC9896192 DOI: 10.1177/23971983221122673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022]
Abstract
Patients with systemic sclerosis and systemic lupus erythematosus serologies present a unique challenge to the clinician when hypertension is detected in the outpatient setting. Treatment choices for non-renal crisis hypertension are different for systemic sclerosis versus systemic lupus erythematosus. Urgent laboratory studies and, in the presence of certain symptoms, imaging assessment are indicated in systemic sclerosis and systemic lupus erythematosus overlap patients with systemic hypertension. Long-term assessment of systemic hypertension may be enhanced by advances in non-contrast imaging that serve as valuable biomarkers for progressive vasculopathy. In this review, the diagnostic approach to systemic sclerosis and systemic lupus erythematosus overlap patients presenting with hypertension is discussed.
Collapse
Affiliation(s)
- Erin Chew
- Division of Rheumatology and
Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville,
TN, USA
| | - April Barnado
- Division of Rheumatology and
Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville,
TN, USA
| | - Talat Alp Ikizler
- Division of Nephrology and
Hypertension, Department of Medicine, Vanderbilt University Medical Center,
Nashville, TN, USA
- Veterans Affair Medical Center,
Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Roy Zent
- Division of Nephrology and
Hypertension, Department of Medicine, Vanderbilt University Medical Center,
Nashville, TN, USA
- Veterans Affair Medical Center,
Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Tracy Frech
- Division of Rheumatology and
Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville,
TN, USA
- Veterans Affair Medical Center,
Tennessee Valley Healthcare System, Nashville, TN, USA
| |
Collapse
|
|
17
|
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
|
|
18
|
Vigneron C, Mouthon L, Chaigne B. Don't mix apples and oranges. Reply to Azoulay et al. Autoimmun Rev 2022; 21:103189. [PMID: 36096469 DOI: 10.1016/j.autrev.2022.103189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 09/04/2022] [Indexed: 11/02/2022]
Affiliation(s)
- Clara Vigneron
- Service de Médecine Intensive-Réanimation, Hôpital Cochin, AP-HP. Centre. 27 rue du Faubourg Saint Jacques, 75014 Paris, France; AP-HP, Centre - Université Paris, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
| | - Luc Mouthon
- AP-HP, Centre - Université Paris, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; Service de Médecine Interne, Centre de Référence Maladies Autoimmunes Systémiques Rares d'Ile de France, Hôpital Cochin, AP-HP, Centre. 27 rue du Faubourg Saint Jacques, 75014 Paris, France
| | - Benjamin Chaigne
- AP-HP, Centre - Université Paris, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; Service de Médecine Interne, Centre de Référence Maladies Autoimmunes Systémiques Rares d'Ile de France, Hôpital Cochin, AP-HP, Centre. 27 rue du Faubourg Saint Jacques, 75014 Paris, France.
| |
Collapse
|
|
19
|
Azoulay LD, Mathian A, Hekimian G, Schmidt M, Luyt CE, Amoura Z, Combes A, Pineton de Chambrun M. Scleroderma cardiac crisis and scleroderma renal crisis: Two sides of the same coin? Clin Exp Rheumatol 2022; 21:103179. [PMID: 35977660 DOI: 10.1016/j.autrev.2022.103179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 08/11/2022] [Indexed: 11/19/2022]
Affiliation(s)
- Levi-Dan Azoulay
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 75013 Paris, France
| | - Alexis Mathian
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 75013 Paris, France
| | - Guillaume Hekimian
- Sorbonne Université, APHP, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, INSERM, UMRS_1166-ICAN, ICAN, Paris, France
| | - Matthieu Schmidt
- Sorbonne Université, APHP, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, INSERM, UMRS_1166-ICAN, ICAN, Paris, France
| | - Charles-Edouard Luyt
- Sorbonne Université, APHP, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, INSERM, UMRS_1166-ICAN, ICAN, Paris, France
| | - Zahir Amoura
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 75013 Paris, France
| | - Alain Combes
- Sorbonne Université, APHP, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, INSERM, UMRS_1166-ICAN, ICAN, Paris, France
| | - Marc Pineton de Chambrun
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, APHP, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Sorbonne Université, INSERM, UMRS_1166-ICAN, ICAN, Paris, France..
| |
Collapse
|
|
20
|
Maritati F, Provenzano M, Lerario S, Corradetti V, Bini C, Busutti M, Grandinetti V, Cuna V, La Manna G, Comai G. Kidney transplantation in systemic sclerosis: Advances in graft, disease, and patient outcome. Front Immunol 2022; 13:878736. [PMID: 35958558 PMCID: PMC9360313 DOI: 10.3389/fimmu.2022.878736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/30/2022] [Indexed: 11/30/2022] Open
Abstract
Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations.
Collapse
|
|
21
|
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
|
|
22
|
Xiong A, Cao Y, Xiang Q, Song Z, Zhang Y, Zhou S, Qiang Y, Chen H, Hu Z, Cui H, Luo J, Wang Y, Yang Y, Yang M, Shuai S. Angiotensin-converting enzyme inhibitors prior to scleroderma renal crisis in systemic sclerosis: A systematic review and meta-analysis. J Clin Pharm Ther 2022; 47:722-731. [PMID: 35233779 DOI: 10.1111/jcpt.13621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/17/2022] [Accepted: 01/27/2022] [Indexed: 02/05/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc. METHODS We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria. RESULTS Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p = 0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p < 0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p = 0.57). WHAT IS NEW AND CONCLUSIONS We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria).
Collapse
Affiliation(s)
- Anji Xiong
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.,Inflammation and Immunology Key Laboratory of Nanchong, Nanchong, Sichuan, China
| | - Yuzi Cao
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Qilang Xiang
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zhuoyao Song
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yan Zhang
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Shifeng Zhou
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yiying Qiang
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Huini Chen
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Ziyi Hu
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Hongxu Cui
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jie Luo
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Ye Wang
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yuan Yang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Min Yang
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Shiquan Shuai
- Department of Rheumatology and Immunology, Nanchong Central Hospital,The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.,Inflammation and Immunology Key Laboratory of Nanchong, Nanchong, Sichuan, China
| |
Collapse
|
|
23
|
Wu Z, Molyneaux PL. Choosing pharmacotherapy for ILD in patients with connective tissue disease. Breathe (Sheff) 2022; 17:210114. [PMID: 35035571 PMCID: PMC8753625 DOI: 10.1183/20734735.0114-2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/23/2021] [Indexed: 11/05/2022] Open
Abstract
Interstitial lung disease (ILD) is a well-recognised complication of several connective tissue diseases (CTD). This article outlines the various treatment options for the most common CTD-ILDs and discuss the ongoing research in this field. https://bit.ly/39NHwx6.
Collapse
Affiliation(s)
- Zhe Wu
- National Heart and Lung Institute, Imperial College London, London, UK.,Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Philip L Molyneaux
- National Heart and Lung Institute, Imperial College London, London, UK.,Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK
| |
Collapse
|
|
24
|
Zanin-Silva DC, Santana-Gonçalves M, Kawashima-Vasconcelos MY, Oliveira MC. Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies. Front Med (Lausanne) 2021; 8:788250. [PMID: 35004754 PMCID: PMC8727451 DOI: 10.3389/fmed.2021.788250] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.
Collapse
Affiliation(s)
- Djúlio César Zanin-Silva
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Basic and Applied Immunology Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Maynara Santana-Gonçalves
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Oncology, Stem Cell and Cell-Therapy Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Marianna Yumi Kawashima-Vasconcelos
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Internal Medicine Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Maria Carolina Oliveira
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| |
Collapse
|
|
25
|
Hughes M, Zanatta E, Sandler RD, Avouac J, Allanore Y. Improvement with time of vascular outcomes in systemic sclerosis: a systematic review and meta-analysis study. Rheumatology (Oxford) 2021; 61:2755-2769. [PMID: 34791057 DOI: 10.1093/rheumatology/keab850] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/15/2021] [Accepted: 11/05/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Vascular disease in systemic sclerosis (SSc) is associated with significant morbidity and mortality. Preliminary data may lead to the suggestion of a modifiable unified-vascular endophenotype. Our aim was to determine whether the prevalence, mortality, and severity of SSc-vascular disease have changed over time. METHODS We performed a systematic review and meta-analysis of the literature in PubMed 1950-2019 related to SSc-digital ulcers (DUs), pulmonary artery hypertension (PAH) and scleroderma renal crisis (SRC). We included full-text articles and extracted study characteristics and assessed risk of bias/quality. We examined the prevalence, mortality, and surrogate measures of SSc-associated vascular disease severity. RESULTS We included 55 studies in our meta-analysis. The pooled prevalence of DUs (41.0%), PAH (9.5%) and SRC (4.9%) remained largely stable over time. There was significant improvement in PAH 1-year (p= 0.001) and SRC mortality (P = <0.001), but not PAH 3-year (p= 0.312) or 5-year (p= 0.686) mortality. The prevalence of DU healing did not significantly change (p= 0.265). There was a trend (all P=∼0.1) towards improvement in PAH surrogates: mean pulmonary artery pressure, pulmonary vascular resistance, and right atrial pressure. For SRC, there was evidence that the overall frequency of dialysis (66.7%, p= 0.297) and permanent dialysis (34.5%, p= 0.036) increased over time. CONCLUSION Despite the heterogeneity and scarcity of the disease, there have been major improvements obtained in the various vascular complications in SSc leading to benefit in survival. This is supported by a trend towards improvement in several surrogate markers and demonstrates that progresses in vascular management translate into major patient benefit.
Collapse
Affiliation(s)
- Michael Hughes
- Department of Rheumatology, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, UK.,Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Elisabetta Zanatta
- Division of Rheumatology, Department of Medicine-DIMED, Padova University Hospital, Padova, Italy
| | - Robert D Sandler
- Department of Rheumatology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals Foundation Trust, Sheffield, UK
| | - Jérôme Avouac
- Rhumatologie, Hôpital Cochin, APHP, Université de Paris, Paris, France
| | - Yannick Allanore
- Department of Rheumatology, Cochin Hospital, AP-HP, Paris Descartes University, Paris, France
| |
Collapse
|
|
26
|
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
|
|
27
|
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
|
|
28
|
Hachulla E, Agard C, Allanore Y, Avouac J, Bader-Meunier B, Belot A, Berezne A, Bouthors AS, Condette-Wojtasik G, Constans J, De Groote P, Diot E, Dumas F, Jego P, Joly F, Launay D, Le Guern V, Le Quintrec JS, Lescaille G, Meune C, Moulin B, Nguyen C, Omeish N, Pene F, Richard MA, Rochefort J, Roren A, Sitbon O, Sobanski V, Truchetet ME, Mouthon L. French recommendations for the management of systemic sclerosis. Orphanet J Rare Dis 2021; 16:322. [PMID: 34304732 PMCID: PMC8310704 DOI: 10.1186/s13023-021-01844-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2021] [Indexed: 12/13/2022] Open
Abstract
Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis.
Collapse
Affiliation(s)
- Eric Hachulla
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence Des Maladies Autoimmunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.
| | - Christian Agard
- Internal Medicine, Nantes University Hospital, University of Nantes, Nantes, France
| | - Yannick Allanore
- Rheumatology Department, Hôpital Cochin, AP-HP, Université de Paris, Paris, France
| | - Jerome Avouac
- Rheumatology Department, Hôpital Cochin, AP-HP, Université de Paris, Paris, France
| | - Brigitte Bader-Meunier
- Department of Pediatric Immunology and Rheumatology; Hospital Necker, APHP, Paris, France
| | - Alexandre Belot
- Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, Bron, France
| | - Alice Berezne
- Department of Internal Medicine, CHR Annecy-Genevois, Annecy, France
| | - Anne-Sophie Bouthors
- Anaesthesia Intensive Care Unit, Jeanne de Flandre Women Hospital, Academic Hospital, ULR 7365 - GRITA - Groupe de Recherche Sur Les Formes Injectables Et Les Technologies Associées, University Lille, Lille, France
| | - Geraldine Condette-Wojtasik
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence Des Maladies Autoimmunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
| | - Joël Constans
- Vascular Medicine Department, Bordeaux University Hospital Centre, Saint André Hospital, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) PeripherAL Artery DIsease Network (PALADIN), Bordeaux, France
| | - Pascal De Groote
- Cardiology Department, Lung-Heart Institute, CHU de Lille, 59000, Lille, France
| | | | - Florence Dumas
- Emergency Department, Cochin Hospital, Paris University, Paris, France
| | - Patrick Jego
- Internal Medicine and Clinical Immunology Unit, CHU Rennes, Rennes, France
| | - Francisca Joly
- Department of Gastroenterology, IBD and Nutrition Support, Beaujon Hospital, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, University of Paris, Clichy, France
| | - David Launay
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence Des Maladies Autoimmunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
| | - Veronique Le Guern
- Service de Médecine Interne, Centre de Référence Maladies Autoimmunes Systémiques Rares D'Ile de France, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), APHP-CUP, Hôpital Cochin, Université de Paris, 75014, Paris, France
| | | | - Geraldine Lescaille
- Centre d'Immunologie et Maladies Infectieuses (CIMI-Paris), Department of Odontology, Paris Diderot/Paris 07, Sorbonne Paris Cité, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Christophe Meune
- Cardiology Department, Hôpital Avicenne, AP-HP, Université de Paris, Paris, France
| | - Bruno Moulin
- Department of Nephrology and Kidney Transplantation, Nouvel Hôpital Civil, University Hospitals of Strasbourg, Strasbourg, France
| | - Christelle Nguyen
- Physical Medicine and Rehabilitation Department, Hôpital Cochin, AP-HP, Université de Paris, Paris, France
| | - Nadine Omeish
- Oral and Dental Medicine, Hôpital Pitié-Salpêtrière, APHP, Université de Paris, Paris, France
| | - Frederic Pene
- Medical Intensive Care Unit, Hôpital Cochin, AP-HP. Centre & Université de Paris, Paris, France
| | - Marie-Aleth Richard
- Department of Dermatology, Timone Hospital, University Hospital of Marseille, Marseille, France
| | - Juliette Rochefort
- Oral and Dental Medicine, Hôpital Pitié-Salpêtrière, APHP, Université de Paris, Paris, France
| | - Alexandra Roren
- AP-HP Cochin Hospital, Université Paris Descartes Sorbonne Paris Cité, INSERM U1153, Paris, France
| | - Olivier Sitbon
- Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Laboratoire d'Excellence en Recherche Sur le Médicament et Innovation Thérapeutique, Université Paris-Sud, Le Kremlin-Bicêtre, France
| | - Vincent Sobanski
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence Des Maladies Autoimmunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
| | | | - Luc Mouthon
- Service de Médecine Interne, Centre de Référence Maladies Autoimmunes Systémiques Rares D'Ile de France, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), APHP-CUP, Hôpital Cochin, Université de Paris, 75014, Paris, France.
| | | |
Collapse
|
|
29
|
Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers. Sci Rep 2021; 11:10679. [PMID: 34021175 PMCID: PMC8139955 DOI: 10.1038/s41598-021-87701-1] [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: 09/21/2020] [Accepted: 03/25/2021] [Indexed: 12/29/2022] Open
Abstract
Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p<0.05, p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p < 0.0001), TGF-β (p < 0.05), IL-8 (p < 0.05), YKL-40 (p < 0.0001) and MMP-7 (p < 0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p < 0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r = = − 0.53, p < 0.01), FVC (%) (r = − 0.51, p < 0.01) and annualized ∆KCO (%) (r = 0.57, p < 0.05), between IS TGF-β levels and annualized ∆FEV-1 (%) (r = = − 0.57, p < 0.05), between IS IGFBP-2 levels and annualized ∆KCO (%) (r = 0.56, p < 0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-β and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.
Collapse
|
|
30
|
Dubourg S, Huck O, Jung S. Implant-based oral rehabilitation in systemic sclerosis patients: a systematic review. J ORAL IMPLANTOL 2021; 48:251-260. [PMID: 33945625 DOI: 10.1563/aaid-joi-d-20-00384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Systemic sclerosis is a rare multisystem autoimmune disorder that significantly impacts the orofacial region. Several oral features including microstomia and increased tooth loss contribute to the mouth-related disability. Prosthetic rehabilitation is very challenging in these patients. As the spectrum of dental implants indications has been recently extended to patients with various systemic disorders, the aim of this systematic review was to evaluate the outcome of dental implants in patients with systemic sclerosis. A literature search was conducted in Medline/PubMed database to identify eligible case-reports. 10 publications were included in qualitative synthesis. A total of 71 implants have been reported in 10 patients with systemic sclerosis with a mean of 7.1 +/- 3.8 implants per patient. Pre-implant surgeries have been described for 3 patients. Implant survival rates were higher than 98% but the mean follow-up time was only 28.3 +/- 18.6 months. Complications have been observed in 3 patients with 1 implant failure and peri-implant bone resorption in 2 patients. Although implant survival rates were high, an individualized assessment of risk-benefit balance is mandatory before indicating implant-based rehabilitation in patients suffering from systemic sclerosis and a scrupulous maintenance program has to be implemented. Further studies are strongly required to establish clinical guidelines.
Collapse
Affiliation(s)
- Sarah Dubourg
- Hôpitaux Universitaires de Strasbourg, Centre de Référence Maladies Rares Orales et Dentaires (O-Rares), Pôle de Médecine et de Chirurgie Bucco-Dentaires - Strasbourg, France
| | - Olivier Huck
- Université de Strasbourg, Faculté de Chirurgie Dentaire - Hôpitaux Universitaires de Strasbourg, Service de Parodontologie et Centre de Référence Maladies Rares Orales et Dentaires - INSERM UMR 1260 - Strasbourg, France
| | - Sophie Jung
- Universite de Strasbourg 1: Universite de Strasbourg Faculté de Chirurgie Dentaire 8 rue Sainte Elisabeth FRANCE STRASBOURG Alsace 67000 Université de Strasbourg, Faculté de Chirurgie Dentaire - Hôpitaux Universitaires de Strasbourg, Centre de Référence Maladies Rares Orales et Dentaires - INSERM UMR_S 1109 - Strasbourg, France
| |
Collapse
|
|
31
|
Scleroderma Renal Crisis in a Case of Mixed Connective Tissue Disease Treated Successfully with Angiotensin-Converting Enzyme Inhibitors. Case Rep Nephrol 2021; 2021:8862405. [PMID: 33505743 PMCID: PMC7808802 DOI: 10.1155/2021/8862405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/10/2020] [Accepted: 12/23/2020] [Indexed: 11/17/2022] Open
Abstract
Mixed connective tissue disease (MCTD) is a rheumatic disease syndrome with overlapping features of scleroderma, systemic lupus erythematosus, and polymyositis. An extremely rare but serious complication that can occur in MCTD is scleroderma renal crisis (SRC). There have been different approaches to the treatment of SRC associated with MCTD. We present a case of MCTD with chronic features of Raynaud's phenomenon, dermatomyositis, and thrombocytopenia complicated with acute SRC which showed a great response to ACE inhibitors. Here, we advise the early and aggressive use of ACE inhibitors as soon as SRC is suspected.
Collapse
|
|
32
|
Alhendi FJ, Werth VP, Sollecito TP, Stoopler ET. Systemic sclerosis: Update for oral health care providers. SPECIAL CARE IN DENTISTRY 2021; 40:418-430. [PMID: 33448431 DOI: 10.1111/scd.12492] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/05/2020] [Accepted: 06/09/2020] [Indexed: 12/22/2022]
Abstract
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease of unknown origin characterized by an uncontrolled inflammatory process resulting in fibrosis of the skin, internal organs and vasculopathy. Manifestations of SSc are heterogenous and can include pulmonary, cardiac, neural, renal, muscular, cutaneous and orofacial complications. Recent scientific advances have led to a better understanding of disease etiopathogenesis and the development of a new classification system. Therapeutic management is often multidisciplinary and targeted toward the affected organs. Oral health care providers (OHCPs) should be familiar with SSc, particularly as it relates to its impact on the orofacial region and modifications to delivery of oral health care for patients with this condition.
Collapse
Affiliation(s)
- Fatmah J Alhendi
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
| | - Victoria P Werth
- Department of Dermatology, Philadelphia V.A. Hospital, Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center, Philadelphia, Pennsylvania
| | - Thomas P Sollecito
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
| | - Eric T Stoopler
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
| |
Collapse
|
|
33
|
Hansrivijit P, Omeonu KF, Lawal HO, Gangireddy M, Gadhiya KP, Dhatt RS. A 45-Year-Old Man with Scleroderma Renal Crisis Associated with a History of Systemic Sclerosis Sine Scleroderma. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e927030. [PMID: 33230093 PMCID: PMC7701023 DOI: 10.12659/ajcr.927030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Patient: Male, 45-year-old Final Diagnosis: Systemic sclerosis sine scleroderma Symptoms: Hypertension • renal failure • shortness of breath Medication: — Clinical Procedure: — Specialty: Nephrology • Rheumatology
Collapse
Affiliation(s)
- Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| | - Kelechi F Omeonu
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| | - Halimat O Lawal
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| | - Mounika Gangireddy
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| | - Kinjal P Gadhiya
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| | - Ravinder S Dhatt
- Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Pinnacle, Harrisburg, PA, USA
| |
Collapse
|
|
34
|
Zhou J, Hou Y, Wang Q, Li M, Zeng X, Xu D. Clinical features and long-term outcomes of Chinese patients with scleroderma renal crisis. Int J Rheum Dis 2020; 23:1194-1200. [PMID: 32700455 DOI: 10.1111/1756-185x.13905] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/05/2020] [Accepted: 06/15/2020] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To investigate the clinical features, treatments, and long-term outcomes of Chinese patients with scleroderma renal crisis (SRC). METHODS We retrospectively reviewed the clinical and laboratory data of 538 patients with systemic sclerosis (SSc) at our center from January 2009 to December 2016, including 29 SRC and 509 SSc without SRC patients. The treatments and long-term outcomes of patients with SRC were also retrospectively analyzed. RESULTS The prevalence of SRC was 5.4% in our cohort. Male gender (odds ratio [OR] =4.194 [95% CI 1.494-11.773]), glucocorticoid exposure (OR = 3.666 [1.484-9.056]), pericardial effusion (OR = 11.180 [4.515-27.681]), and myocardial involvement (OR = 7.958 [1.664-38.064]) were associated with an increased risk of development of SRC. Despite the wide use of angiotensin-converting enzyme inhibitors, the permanent dialysis rate of patients with SRC was 48.3%. Sixteen patients died during follow-up, and the estimated 1- and 5-year survival rates of patients with SRC were 62.1% and 47.3%, respectively. Withdrawal of dialysis (5 patients) and myocardial complications (3 patients) were the main causes of death in patients with SRC. Patients with serum creatinine level >500 µmol/L before treatment (log rank test 5.051, P = 0.025) and/or those who needed dialysis at the onset of SRC (log rank test 12.870, P < 0.001) showed poorer prognosis. CONCLUSION SRC is a rare but severe complication in patients with SSc. Male gender, glucocorticoid exposure, pericardial effusion, and myocardial involvement were risk factors in the development of SRC. Withdrawal of dialysis and myocardial complications were the main causes of death in Chinese patients with SRC.
Collapse
Affiliation(s)
- Jiaxin Zhou
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Yong Hou
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Dong Xu
- Department of Rheumatology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| |
Collapse
|
|
35
|
Andrade López AC, Bande Fernández JJ, Colunga Argüelles D, Gómez de la Torre R. Scleroderma Renal Crisis: the Experience of a Third-Level Hospital. REUMATOLOGIA CLINICA 2020; 16:306-307. [PMID: 29929809 DOI: 10.1016/j.reuma.2018.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 04/08/2018] [Accepted: 04/18/2018] [Indexed: 06/08/2023]
Affiliation(s)
- Ana C Andrade López
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España.
| | | | - Dolores Colunga Argüelles
- Servicio de Medicina Interna, Unidad de Enfermedades Sistémicas Autoinmunes, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| | - Ricardo Gómez de la Torre
- Servicio de Medicina Interna, Unidad de Enfermedades Sistémicas Autoinmunes, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| |
Collapse
|
|
36
|
Chrabaszcz M, Małyszko J, Sikora M, Alda-Malicka R, Stochmal A, Matuszkiewicz-Rowinska J, Rudnicka L. Renal Involvement in Systemic Sclerosis: An Update. Kidney Blood Press Res 2020; 45:532-548. [PMID: 32521536 DOI: 10.1159/000507886] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 04/14/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. SUMMARY Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients' outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.
Collapse
Affiliation(s)
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland,
| | - Mariusz Sikora
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| | | | - Anna Stochmal
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| | | | - Lidia Rudnicka
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
|
37
|
Kurteva EK, Boyadzhieva VV, Stoilov NR. Systemic sclerosis in mother and daughter with susceptible HLA haplotype and anti-topoisomerase I autoantibodies. Rheumatol Int 2020; 40:1001-1009. [PMID: 31970496 DOI: 10.1007/s00296-020-04516-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 01/08/2020] [Indexed: 01/08/2023]
Abstract
Systemic sclerosis is a rare systemic autoimmune rheumatic disease which is thought to be polygenic disorder contributed by both genetic and environmental factors. A positive family history of SSc is the strongest risk factor yet identified for SSc; however, the absolute risk for each family member remains quite low. A systematic literature search was performed in MEDLINE and Scopus database for studies published only in English that investigated the prevalence of SSc in first-degree relatives of SSc patients and whether SSc family members have greater frequency of I autoantibodies (ATA) than expected. Following keywords and terms: "systemic sclerosis", "scleroderma", "familial","ATA", "topoisomerase", and "anti-Scl70" were used to select the appropriate articles. From the 21 initially identified articles, 16 were eliminated because of the inclusion criteria, and five articles concerning familial occurrence of SSc in first-degree relatives positive for ATA were included for further analysis. Two case reports were described-a daughter and a mother diagnosed with systemic sclerosis with ATA tested for specific genotype. In both cases, patients had antinuclear autoantibodies (ANA) at a titer of > 1:1280, AC-29 cell pattern according to ICAP, and their sera were positive for ATA. In addition, anti-SSA/Ro60 autoantibodies were found in the case of the mother. Complementary to ATA positivity, the daughter was also positive for AMA-M2 autoantibodies. The results showed that our patients shared HLA-DRB1*1104-DQA1*0501-DQB1*0301 haplotype and had positive ATA, which corresponds to the strong association between ATA in white subjects and HLA-DRB1*1104, DQA1*0501, DQB1*0301 haplotype (OR = 6.93). Our patients not only shared a risky HLA haplotype for SSc but also manifested with a similar immunological activity, given that they were both positive for ATA. Although infrequent, ATA-positive SSc patients could develop scleroderma renal crisis, as in the case of the mother. Therefore, careful monitoring of the renal function is the best strategy for the case of the daughter. A positive family history is an important hint for patients suspected of autoimmune disease. The cases of familial SSc are quite rare, but they give us the opportunity to compare the genetic background, environmental risk factors, SSc phenotype, ANA type, and prevention of the complications in the course of the disease.
Collapse
Affiliation(s)
- Ekaterina Krasimirova Kurteva
- Laboratory of Clinical Immunology, Department of Clinical Immunology, University Hospital "St. Ivan Rilski", Medical University of Sofia, Ivan Geshov Str. 15, 1431, Sofia, Bulgaria
| | - Vladimira Vasileva Boyadzhieva
- Department of Internal Medicine, Clinic of Rheumatology, University Hospital "St. Ivan Rilski", Medical University of Sofia, 13 Urvich Str., 1612, Sofia, Bulgaria.
| | - Nikolay Rumenov Stoilov
- Department of Internal Medicine, Clinic of Rheumatology, University Hospital "St. Ivan Rilski", Medical University of Sofia, 13 Urvich Str., 1612, Sofia, Bulgaria
| |
Collapse
|
|
38
|
Systemic sclerosis and end-stage renal disease: study of patient characteristics, follow-up and outcomes in France. J Nephrol 2020; 34:617-625. [PMID: 32449084 DOI: 10.1007/s40620-020-00746-9] [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: 12/19/2019] [Accepted: 05/11/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Scleroderma renal crisis (SRC), the most frequent renal complication of Systemic Sclerosis (SSc), can lead to end-stage renal disease (ESRD), most frequently, but not exclusively, because of scleroderma renal crisis (SRC). METHODS The main objectives of our study using data extracted from the French renal epidemiology and information network (REIN) registry, were to describe the characteristics and outcomes in an incident French cohort of SSc patients requiring renal replacement therapy (RRT) compared with a matched RRT patient sample. RESULTS Between 2002 and 2014, 120 incident SSc patients started RRT in France. SSc was significantly associated with higher mortality (HR 1.95; 95% CI 1.41-2.71; p = 0.001) in comparison with matched controls. Among SSc patients in dialysis, besides age, the only risk factor independently associated with mortality was the inability to walk without help (HR 2.34, CI 95% 1.37-4.02, p = 0.002). Dialysis withdrawal was reported for 22 (18.3%) of the SSc patients compared to 15 (6.3%) for the controls. Patients with SSc have less access to transplantation waiting list (HR 0.21; CI 95% 0.11-0.41, p < 0.001) and to kidney transplantation (KTR) (HR 0.22; 95% CI 0.12-0.43; p < 0.001). During the follow-up, 6 of the 27 patients (22.2%) registered on KTR waiting list died compared to 69 of the 93 (74.2%) patients who were not on the waiting list. CONCLUSIONS The prognosis for SSc patients requiring RRT is still poor, with a significantly higher mortality and lower registration on kidney transplant waiting-list compared to matched controls.
Collapse
|
|
39
|
Yamashita H, Kamei R, Kaneko H. Classifications of scleroderma renal crisis and reconsideration of its pathophysiology. Rheumatology (Oxford) 2020; 58:2099-2106. [PMID: 31566243 DOI: 10.1093/rheumatology/kez435] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/25/2019] [Indexed: 11/14/2022] Open
Abstract
Categorization of scleroderma renal crisis (SRC) as hypertensive or normotensive can potentially overlook the underlying pathophysiology that might be unique in each patient, as they often exhibit a mixture of distinct pathological characteristics of narrowly defined SRC (nd-SRC) and systemic sclerosis associated thrombocytic micro-angiopathy (SSc-TMA). In this review, we provide evidence suggesting that better categorization of patients presenting with certain clinical features of both nd-SRC and TMA will improve treatment approaches. Based on our clinical experience and literature review, distinguishing between nd-SRC and SSc-TMA is important because the association of SSc-TMA with prior steroid administration and poor prognosis was stronger than that of nd-SRC. Although the two pathological entities cannot be easily distinguished based on blood pressure, we suggest that the detailed clinical course is helpful. Typically, nd-SRC exhibits prominently elevated blood pressure and worsening of renal function initially, followed by mild thrombocytopenia. Conversely, SSc-TMA presents first with severe thrombocytopenia, followed by elevated blood pressure and renal function deterioration. The degree of involvement in each pathological condition should be considered for determination of appropriate therapeutic interventions and prognostic prediction.
Collapse
Affiliation(s)
- Hiroyuki Yamashita
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Ryosuke Kamei
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Hiroshi Kaneko
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| |
Collapse
|
|
40
|
Abstract
PURPOSE OF REVIEW Scleroderma renal crisis (SRC) is a life-threatening manifestation in systemic sclerosis (SSc) and is usually presented by an acute onset of severe hypertension together with an acute kidney injury. We can conceptualize SRC as a systemic syndrome with features that extend beyond the involvement of the kidney. The goal of this review is to inform clinicians about the risk factors for SRC in patients with SSc and to emphasize the importance of early identification and initiation of treatment. RECENT FINDINGS For the past 3 decades, the use of angiotensin-converting enzyme inhibitors (ACE-I) to treat SRC, has been rightfully synonymized with a good outcome, and has changed the trajectory of mortality in SRC. Despite this, SRC still figures in one of the top four causes of mortality in patients with SSc. There is a need for additional therapeutic agents to treat SRC that is refractory to ACE-I. There has been a recent interest in combining ACE-I with endothelin receptor blockers and agents targeting the complement component 5. There is no role for using ACE-I prophylactically in high-risk patients. SUMMARY Early diagnosis of SRC is the key, and early initiation of ACE-I is life-saving and associated with a better prognosis. We should consider renal transplantation in selected patients, especially those on long-term dialysis.
Collapse
|
|
41
|
Cao XY, Liu H, Xu D, Li MT, Wang Q, Jiang L, Hou Y, Zhu LX, Zeng XF. Patterns of renal pathology in Chinese patients with systemic sclerosis undergoing renal biopsy at a tertiary medical center. J Int Med Res 2020; 48:300060519894456. [PMID: 31878823 PMCID: PMC7783277 DOI: 10.1177/0300060519894456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 11/21/2019] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE We investigated renal injury characteristics in Chinese patients with systemic sclerosis (SSc) who had undergone renal biopsy. METHODS We searched the medical records of patients with SSc who were hospitalized at Peking Union Medical College Hospital between January 1990 and August 2019. We analyzed the clinical characteristics and pathological results of these patients. RESULTS We identified 25 patients who had undergone renal biopsy. Of these patients, 10 had scleroderma renal crisis (SRC); one underwent renal biopsy twice (for diffuse mesangial proliferative glomerulonephritis and for SRC); two had antineutrophil cytoplasmic antibody-associated glomerulonephritis; one had immunoglobulin M nephropathy; one had minimal change nephropathy; seven had lupus nephritis; one had scleroderma renal crisis with comorbid lupus nephritis; and two had drug-related kidney injury (caused by aristolochic acid in one and D-penicillamine in the other). Acute tubular necrosis was observed in the patient taking oral aristolochic acid, while minimal change nephropathy was observed in the patient with D-penicillamine-induced renal injury. CONCLUSIONS SRC was the most commonly encountered renal damage in patients with SSc. We recommend biopsy for patients undergoing treatment for SRC who have persistent renal injury with proteinuria, regardless of hematuria. Rheumatologists in Eastern countries should be aware of aristolochic acid nephropathy.
Collapse
Affiliation(s)
- Xiao-yu Cao
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - He Liu
- Department of Ultrasound, Peking
Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking
Union Medical College, Beijing, China
| | - Dong Xu
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Meng-tao Li
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Qian Wang
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Li Jiang
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Yong Hou
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| | - Li-xiu Zhu
- Department of Rheumatology, Ningde
Hospital Affiliated to Fujian Medical University, Ningde, Fujian Province,
China
| | - Xiao-feng Zeng
- Department of Rheumatology and
Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of
Medical Sciences & Peking Union Medical College, Graduate School of Peking
Union Medical College, Beijing, China
| |
Collapse
|
|
42
|
Honda S, Katsumata Y, Karasawa K, Yamanaka H, Harigai M. Management of End-stage Renal Disease Associated with Systemic Rheumatic Diseases. JMA J 2020; 3:20-28. [PMID: 33324772 PMCID: PMC7733740 DOI: 10.31662/jmaj.2019-0020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 07/22/2019] [Indexed: 11/15/2022] Open
Abstract
The outcomes of rheumatic diseases (RDs) have improved over the past decades. However, a significant proportion of the patients still suffer from end-stage renal disease (ESRD) and have to bear the burden of hemodialysis. It is crucial to prevent patients with RDs from developing ESRD from viewpoints of medicine and medical economics. For those who already have ESRD, it is important to improve vial prognosis and quality of life through appropriate management of disease activity and comorbidities related to ESRD. Thus, rheumatologists and nephrologists need to recognize risk factors associated with progression to ESRD along with their appropriate management. Although the activity of most RDs tends to decrease after initiation of hemodialysis, disease activity may still increase, and recognizing how to appropriately use immunosuppressive agents even after the development of ESRD is crucial. The treatment of RDs needs extra attention as hydroxychloroquine requires more frequent monitoring for adverse drug reactions; therapeutic drug monitoring is necessary for mycophenolate mofetil, cyclosporine A, and tacrolimus; cyclophosphamide and azathioprine need dose adjustments; methotrexate and bucillamine are contraindicated in patients with ESRD; leflunomide and sulfasalazine do not require significant dose reduction and iguratimod should be carefully administered. The pharmacokinetics of biological agents such as rituximab or belimumab are not affected by ESRD, and dose adjustments are not necessary. Collaboration between rheumatologists and nephrologists is needed more than ever and is expected to produce a complementary effect and achieve better outcomes in clinical settings, although this cooperation has not always been conducted appropriately.
Collapse
Affiliation(s)
- Suguru Honda
- Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Yasuhiro Katsumata
- Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunori Karasawa
- Department of Nephrology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Hisashi Yamanaka
- Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Masayoshi Harigai
- Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
- Division of Epidemiology and Pharmacoepidemiology, Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| |
Collapse
|
|
43
|
Acute Heart Failure in Scleroderma Renal Crisis: A Case Study for Review of Cardiac Disease in Systemic Sclerosis. AMERICAN JOURNAL OF MEDICAL CASE REPORTS 2020; 8:1-7. [PMID: 31773058 PMCID: PMC6878899 DOI: 10.12691/ajmcr-8-1-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
|
|
44
|
Joubert M, Olagne L, Smets P, Outh R, Garrouste C, Lautrette A, Hermet M, Aumaître O, Andre M. Série de six patients atteints de crise rénale sclérodermique. Rev Med Interne 2019. [DOI: 10.1016/j.revmed.2019.10.207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
45
|
Blagojevic J, Legendre P, Matucci-Cerinic M, Mouthon L. Is there today a place for corticosteroids in the treatment of scleroderma? Autoimmun Rev 2019; 18:102403. [DOI: 10.1016/j.autrev.2019.102403] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 07/11/2019] [Indexed: 12/21/2022]
|
|
46
|
Salituri J, Patey N, Takano T, Fiset P, Del Rincon S, Berkson L, Baron M, Hudson M, Baron M, Hudson M, Gyger G, Pope J, Larché M, Khalidi N, Masetto A, Sutton E, Robinson D, Rodriguez-Reyna T, Smith D, Thorne C, Fortin P, Fritzler M. Mammalian target of rapamycin is activated in the kidneys of patients with scleroderma renal crisis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2019; 5:152-158. [DOI: 10.1177/2397198319885488] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 10/04/2019] [Indexed: 12/12/2022]
Abstract
Objectives: Scleroderma renal crisis is a rare but serious complication affecting 2%–15% of patients with systemic sclerosis. Despite treatment with angiotensin-converting enzyme inhibitors, outcomes for scleroderma renal crisis patients are still poor. The cellular signaling mechanisms in scleroderma renal crisis are not yet known. Mammalian target of rapamycin, comprised of the subunits mTORC1 and mTORC2, has been shown to be activated in vascular lesions of renal transplant patients with anti-phospholipid antibody syndrome. Given the similarities between the pathophysiology of scleroderma renal crisis and anti-phospholipid antibody syndrome, we hypothesized that the mammalian target of rapamycin pathway would also be activated in the renal vasculature of patients with scleroderma renal crisis. Methods: We retrospectively analyzed renal biopsies of five patients with scleroderma renal crisis in the Canadian Scleroderma Research Group cohort. Immunostaining was performed using anti-P-S6RP antibodies to evaluate the phosphorylation of mTORC1, and anti-Rictor and anti-S473 to determine activation of mTORC2. Results: Four of the five patients showed mTORC1 activation in arteriolar endothelial cells, and three of the five patients showed mTORC1 activation in the arterial endothelial cells. Two of four samples showed Rictor expression in the arteriolar and arterial endothelial cells, showing mTORC2 activation. There was no expression of mTORC1 or mTORC2 in samples from two healthy controls. Conclusion: We demonstrate that both mTORC1 and mTORC2 are activated in renal biopsies with typical histologic features of scleroderma renal crisis. Dual mammalian target of rapamycin inhibitors are currently available and in development. These findings could inform further research into novel treatment targets for scleroderma renal crisis.
Collapse
Affiliation(s)
| | - Natalie Patey
- Department of Pathology, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada
| | - Tomoko Takano
- Department of Medicine, McGill University, Montreal, QC, Canada
- Department of Medicine, McGill University Health Center, Montreal, QC, Canada
| | - Pierre Fiset
- Department of Medicine, McGill University Health Center, Montreal, QC, Canada
| | | | - Laeora Berkson
- Department of Medicine, McGill University, Montreal, QC, Canada
- Division of Rheumatology, Jewish General Hospital, Montreal, QC, Canada
| | - Murray Baron
- Department of Medicine, McGill University, Montreal, QC, Canada
- Division of Rheumatology, Jewish General Hospital, Montreal, QC, Canada
| | - Marie Hudson
- Department of Medicine, McGill University, Montreal, QC, Canada
- Lady Davis Institute, Montreal, QC, Canada
- Division of Rheumatology, Jewish General Hospital, Montreal, QC, Canada
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Jacquier M, Mousson C, Rebibou JM, Lakomy D, François S, Martin L, Funes De La Vega M, Legendre M. Scleroderma Renal Crisis in a Systemic Sclerosis With Anti-PM/Scl Antibodies. Kidney Int Rep 2019; 4:1499-1502. [PMID: 31701063 PMCID: PMC6829186 DOI: 10.1016/j.ekir.2019.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 06/25/2019] [Accepted: 07/01/2019] [Indexed: 11/29/2022] Open
Affiliation(s)
- Marine Jacquier
- Department of Nephrology, François Mitterand Hospital, Dijon, France
| | | | | | - Daniela Lakomy
- Department of Immunology, François Mitterand Hospital, Dijon, France
| | | | - Laurent Martin
- Department of Pathology, François Mitterand Hospital, Dijon, France
| | | | - Mathieu Legendre
- Department of Nephrology, François Mitterand Hospital, Dijon, France
| |
Collapse
|
|
48
|
Singh JA, Cleveland JD. Systemic sclerosis is associated with knee arthroplasty outcomes: a National US study. Clin Rheumatol 2019; 39:85-92. [PMID: 31444650 DOI: 10.1007/s10067-019-04754-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/01/2019] [Accepted: 08/15/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVE To assess whether systemic sclerosis (SSc) is associated with total knee arthroplasty (TKA) outcomes. METHODS We used the 1998-2014 US National Inpatient Sample. We conducted multivariable-adjusted logistic regression analyses to examine the association of a diagnosis of SSc with post-TKA in-hospital complications (implant infection, revision, transfusion, mortality) and healthcare utilization (hospital charges, hospital stay, non-home vs. home discharge). Odds ratios (OR) and 95 % confidence intervals (CI) were calculated. RESULTS Our cohort included 8,123,388 people without SSc and 3894 people with SSc. In multivariable-adjusted analyses, compared to people without SSc, people with SSc had higher odds of transfusion, hospital stay > 3 days and non-home discharge with higher OR of 1.42 (95 % CI, 1.20, 1.69), 1.29 (95 % CI, 1.11, 1.49), and 1.29 (95 % CI, 1.11, 1.49), respectively. No differences were seen in revision, 0.68 (95 % CI, 0.10, 4.69) or hospital charges above the median, 1.01 (95 % CI, 0.70, 1.46). Differences in implant infection or mortality were not estimable, since none of the patients with SSc had implant infection or died. Sensitivity analyses that adjusted the main analysis additionally for hospital-level variables confirmed study findings with minimal or no attenuation of OR. CONCLUSION SSc was associated with higher risk of transfusion and increased healthcare utilization after TKA. Future studies should examine if interventions can address modifiable factors to further optimize these outcomes.Key Points• Systemic sclerosis was independently associated with higher healthcare utilization after TKA.• The adjusted odds of transfusion was higher in people with systemic sclerosis compared to those without systemic sclerosis who underwent TKA.
Collapse
Affiliation(s)
- Jasvinder A Singh
- Birmingham Veterans Affairs (VA) Medical Center, Birmingham, AL, USA. .,Department of Medicine at the School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. .,Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
| | - John D Cleveland
- Department of Medicine at the School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| |
Collapse
|
|
49
|
Gordon SM, Hughes JB, Nee R, Stitt RS, Bailey WT, Little DJ, Edison JD, Olson SW. Systemic sclerosis medications and risk of scleroderma renal crisis. BMC Nephrol 2019; 20:279. [PMID: 31345158 PMCID: PMC6659266 DOI: 10.1186/s12882-019-1467-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 07/17/2019] [Indexed: 01/13/2023] Open
Abstract
Background Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. Methods In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls. Results ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6–10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1–29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC. Conclusion ACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.
Collapse
Affiliation(s)
- S M Gordon
- Nephrology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA
| | - J B Hughes
- Department of Medicine, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, USA
| | - R Nee
- Nephrology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA
| | - R S Stitt
- Rheumatology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, USA
| | - W T Bailey
- Rheumatology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, USA
| | - D J Little
- Nephrology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA
| | - J D Edison
- Rheumatology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, USA
| | - S W Olson
- Nephrology Department, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA.
| |
Collapse
|
|
50
|
Montrief T, Koyfman A, Long B. Scleroderma renal crisis: a review for emergency physicians. Intern Emerg Med 2019; 14:561-570. [PMID: 31076978 DOI: 10.1007/s11739-019-02096-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 04/27/2019] [Indexed: 12/15/2022]
Abstract
Scleroderma renal crisis (SRC) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization. This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of SRC. While SRC remains a rare clinical presentation, surveillance data suggest an overall incidence between 4 and 6% of patients with scleroderma. The diagnostic criteria for SRC include a new onset blood pressure > 150/85 mm Hg OR increase ≥ 20 mm Hg from baseline systolic blood pressure, along with a decline in renal function, defined as an increase serum creatinine of ≥ 10% and supportive features. There are many risk factors for SRC, including diffuse and rapidly progressive skin thickening, palpable tendon friction rubs, and new anemia or cardiac events. Critical patients should be evaluated in the resuscitation bay, and consultation with the nephrology team for appropriate patients improves patient outcomes.
Collapse
MESH Headings
- Angiotensin-Converting Enzyme Inhibitors/therapeutic use
- Antibodies, Antineutrophil Cytoplasmic/analysis
- Antibodies, Antineutrophil Cytoplasmic/blood
- Emergency Service, Hospital/organization & administration
- Humans
- Kidney Failure, Chronic/drug therapy
- Kidney Failure, Chronic/etiology
- Kidney Failure, Chronic/physiopathology
- Purpura, Thrombotic Thrombocytopenic/blood
- Purpura, Thrombotic Thrombocytopenic/diagnosis
- Purpura, Thrombotic Thrombocytopenic/physiopathology
- Renal Dialysis/methods
- Risk Factors
- Scleroderma, Systemic/blood
- Scleroderma, Systemic/complications
- Scleroderma, Systemic/physiopathology
Collapse
Affiliation(s)
- Tim Montrief
- Department of Emergency Medicine, Jackson Memorial Hospital/Miller School of Medicine, University of Miami, 1611 N.W. 12th Avenue, Miami, FL, 33136, USA
| | - Alex Koyfman
- Department of Emergency Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA
| | - Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, 3841 Roger Brooke Dr, Fort Sam Houston, TX, 78234, USA.
| |
Collapse
|