scholarly journals A Japanese Patient with Anti-PM/Scl and Centromere Antibody-Positive Scleroderma-Amyopathic Dermatomyositis Overlap Syndrome Who Developed Renal Crisis

2021 ◽  
Author(s):  
Tomoya Nishida ◽  
Kazuhisa Nakano ◽  
Minoru Satoh ◽  
Shunsuke Fukuyo ◽  
Koichi Akashi ◽  
...  
Keyword(s):  
Strong Association ◽  
Rna Polymerase Iii ◽  
Japanese Patients ◽  
The United States ◽  
Overlap Syndrome ◽  
Scleroderma Renal Crisis ◽  
Amyopathic Dermatomyositis ◽  
Old Japanese ◽  
Anticentromere Antibodies ◽  
Renal Crisis

Abstract Anti-PM/Scl antibodies are associated with the overlap syndrome of systemic sclerosis and dermatomyositis/polymyositis (SSc-DM/PM), and are found in 50% of SSc-DM/PM cases in Europe and the United States, whereas they are rare in Japan. We report a case of an 80-year-old Japanese female with SSc-amyopathic dermatomyositis (ADM) overlap syndrome, who developed scleroderma renal crisis (SRC), a complication of SSc. She had positive antinuclear antibodies in a discrete-speckled and nucleolar pattern and anticentromere antibodies and anti-PM/Scl antibodies were confirmed by ELISA and immunoprecipitation, respectively. The incidence rate of SRC in SSc patients varies significantly depending on the specificity of autoantibodies, with the highest incidence of ~50% in anti-RNA polymerase III antibody positive patients, followed by ~10% in anti-PM/Scl and lower incidence of 0.45% in anticentromere antibody-positive cases. Anti-PM/Scl antibodies are uncommon in Japanese patients presumably due to its strong association with certain HLA haplotype that is rare in Japanese. Clinical significance of anti-PM/Scl antibodies in Japanese patients will need to be clarified with accumulation of cases in future studies.

Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis

2020 ◽  
Vol 47 (11) ◽  
pp. 1668-1677
Author(s):  
Edward P. Stern ◽  
Sandra G. Guerra ◽  
Harry Chinque ◽  
Vanessa Acquaah ◽  
David González-Serna ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Renal Biopsy ◽  
Genetic Susceptibility ◽  
Rna Polymerase Iii ◽  
Human Kidney ◽  
Scleroderma Renal Crisis ◽  
Nucleotide Polymorphisms ◽  
Polymerase Iii ◽  
Renal Crisis

ObjectiveScleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC.MethodsARA-positive patients (n = 99) with at least 5 years’ follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort.ResultsAnalysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10−5), CTNND2 (rs1859082; P = 5.58 × 10−5), HECW2 (rs16849716; P = 1.2 × 10−4), and GPATCH2L (rs935332; P = 4.92 × 10−5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP.ConclusionIncreased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

Scleroderma Renal Crisis

2014 ◽  
Vol 41 (6) ◽  
pp. 1040-1048 ◽  
Author(s):  
Luc Mouthon ◽  
Guillaume Bussone ◽  
Alice Berezné ◽  
Laure-Hélène Noël ◽  
Loïc Guillevin
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Antihypertensive Drugs ◽  
Rna Polymerase Iii ◽  
Pressure Control ◽  
Hypertensive Encephalopathy ◽  
Left Ventricular ◽  
Scleroderma Renal Crisis ◽  
Volume Depletion ◽  
Renal Crisis

Scleroderma renal crisis (SRC) is characterized by malignant hypertension and oligo-anuric acute renal failure. It occurs in 5% of patients with systemic sclerosis (SSc), particularly in patients with diffuse disease during the first years. SRC is more common in patients receiving corticosteroids, the risk increasing with increasing dose. The disease is sometimes triggered by use of nephrotoxic drugs and/or intravascular volume depletion. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43% of cases, and anti-RNA-polymerase III antibodies are present in one-third of patients. Renal biopsy is not necessary if SRC presents classical features. However, biopsy may help to define the prognosis and guide treatment in atypical forms. The prognosis of SRC has greatly improved with the introduction of angiotensin-converting enzyme (ACE) inhibitors. However, the 5-year survival for SSc patients with full SRC remains low (65%). The treatment of SRC relies on aggressive blood pressure control with an ACE inhibitor, combined with other antihypertensive drugs if needed. Dialysis is frequently indicated but can be stopped in about half of patients, mainly those with good blood pressure control. Patients who need dialysis for more than 2 years qualify for renal transplantation.

scholarly journals Prevalence, Correlates and Outcomes of Gastric Antral Vascular Ectasia in Systemic Sclerosis: A EUSTAR Case-control Study

2013 ◽  
Vol 41 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Etienne Ghrénassia ◽  
Jérome Avouac ◽  
Dinesh Khanna ◽  
Chris T. Derk ◽  
Oliver Distler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Gastric Antral Vascular Ectasia ◽  
Vascular Ectasia ◽  
Polymerase Iii ◽  
European League Against Rheumatism ◽  
Vascular Phenotype ◽  
Renal Crisis

Objective.To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).Methods.We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes.Results.Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01).Conclusion.GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

scholarly journals Clinical and Immunologic Predictors of Scleroderma Renal Crisis in Japanese Systemic Sclerosis Patients With Anti-RNA Polymerase III Autoantibodies

2015 ◽  
Vol 67 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Yasuhito Hamaguchi ◽  
Masanari Kodera ◽  
Takashi Matsushita ◽  
Minoru Hasegawa ◽  
Yuki Inaba ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis

Abstract P244: Scleroderma Renal Crisis Among Systemic Sclerosis Patients; A Large Cohort Study From The United States National Emergency Department Database.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Mohammed Uddin ◽  
Tanveer Mir ◽  
Obaid Shafi ◽  
Hamza Tahir ◽  
Sarvani Surapaneni ◽  
...  
Keyword(s):  
United States ◽  
Emergency Department ◽  
Systemic Sclerosis ◽  
The United States ◽  
Scleroderma Renal Crisis ◽  
Vein Thrombosis ◽  
Incidence And Mortality ◽  
National Emergency ◽  
Deep Vein ◽  
Renal Crisis

Background: Literature regarding trends for incidence and mortality of Scleroderma renal crisis (SRC) in systemic sclerosis (SSc) within the United States (US) emergency departments (ED) is limited. Objective: To study the trends for incidence and mortality of SRC among SSc patient encounters within the US EDs. Methods: Data from the national emergency department sample (NEDS) constitutes 20% sample of hospital-owned EDs and in-patient sample in the United States. All ED encounters were included in the analysis. Major complications related to each ED encounter were obtained by using ICD codes. A Linear p-trend was used to assess the trends. Results: Of the total 180,435 ED encounters with a diagnosis of SSc in NEDS for the years 2009-2014, 771 (4.27/1,000) (mean age of 59.6 ± 15.5 years, 75.4% females) patients were recorded with SRC. A total of 32 (4.1%) patients had died during these ED hospital encounters. The SSc with SRC subgroup was associated with higher rates of life-threatening complications when compared to SSc without the SRC subgroup. Cerebrovascular complications include acute ischemic stroke 44 (5.6%). Cardiac complications include new-onset atrial fibrillation 62 (8%), conduction block 13 (1.6%) and acute onset heart failure 186 (24.1%). Other complications include pulmonary arterial hypertension 122 (15.8%), respiratory failure 212 (27.5%), and deep vein thrombosis 36 (4.7%). The yearly trend for the incidence of SRC every 1,000 ED SSc encounters in the United States increased over the study years from 2.11/1,000 in 2009 to 5.79/1,000 in 2014 (linear p-trend 0.002). The yearly trend for the mortality related to SRC in the United States remained steady over the study years 2009-2014 (linear p-trend 0.3187). Conclusion: SRC is a relatively rare medical emergency among patients with SSc. Although there has been a significant rise in the incidence of SRC among SSc patients over the study years, mortality rates had remained steady. Proper management of the underlying risk factors can prevent the development of SRC and associated complications. Keywords: Systemic sclerosis, Scleroderma renal crisis, pulmonary hypertension, deep vein thrombosis.

Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

2009 ◽  
Vol 37 (1) ◽  
pp. 125-130 ◽  
Author(s):  
OLIVIER MEYER ◽  
LUC DE CHAISEMARTIN ◽  
PASCALE NICAISE-ROLAND ◽  
JEAN CABANE ◽  
FLORENCE TUBACH ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
The United States ◽  
Cutaneous Disease ◽  
Polymerase Iii ◽  
Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

scholarly journals 320. The Prognosis of Scleroderma Renal Crisis in RNA-Polymerase III Antibody-Positive Compared to Rna-Polymerase III Antibody-Negative Patients

Rheumatology ◽  
2014 ◽  
Vol 53 (suppl_1) ◽  
pp. i179-i179 ◽  
Author(s):  
Bernadette M. Lynch ◽  
Henry Penn ◽  
Jennifer Harvey ◽  
Aine Burns ◽  
Christopher P. Denton
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis

scholarly journals Scleroderma nephropathy: unsolved problems

2021 ◽  
Vol 7 (5) ◽  
pp. 5-18
Author(s):  
I. E. Bulavko ◽  
E. V. Timofeev ◽  
K. J. U. Alkak ◽  
V. A. Isakov
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Systemic Sclerosis ◽  
Rna Polymerase Iii ◽  
Kidney Injury ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme Inhibitors ◽  
Treatment Approaches ◽  
Renal Crisis

Kidney injury is a common pathology in the group of patients with systemic sclerosis. At least half of the patients show histological signs of it. Acute condition is known as scleroderma renal crisis. Although discussions regarding the risk factors for scleroderma renal crisis are open, most researchers consider the following factors: female sex, previous proteinuria and hypertension, the presence of anti-RNA polymerase III antibodies, and a decrease in lung diffusion capacity ≤75%. Diagnostic criteria for scleroderma renal crisis include an acute increase in blood pressure, accompanied by acute renal failure and abnormalities in the urinary sediment, anemia, and thrombocytopenia. Treatment of scleroderma renal crisis entails decreasing blood pressure, mainly with short-acting angiotensin-converting enzyme inhibitors, followed by selecting effective antihypertensive therapy. Further research of new treatment approaches is being carried on: the use of endothelin receptor antagonists (bosentan), monoclonal antibodies against the complement component 5 (eculizumab). Despite the approved strategies for identifying risk factors for scleroderma renal crisis development and treatment approaches, this group of patients is still characterized by high rates of mortality, the need for renal replacement therapy, and kidney transplantation. Thus, the problem of kidney injury in systemic sclerosis remains relevant.

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