Development Of Scleroderma Renal Crisis Research Articles

AB0653 The association of autoantibodies with morbidity and mortality of scleroderma renal crisis in Japan

BackgroundThe morbidity of scleroderma renal crisis (SRC) and autoantibodies in systemic sclerosis (SSc) vary by races and regions. Anti-RNA polymerase III is associated with SRC in America and European countries. However, the association of autoantibodies with SRC had not been elucidated in Japan.ObjectivesWe aimed to investigate the association of autoantibodies with morbidity and mortality of SRC in Japan.MethodsThe clinical characteristics and mortality of 330 patients with systemic sclerosis (SSc) at Kyoto University Hospital were retrospectively analyzed, focusing on anti-centromere, anti-RNA polymerase III, anti-topoisomerase I, and anti-U1-RNP. Logistic regression analyses were performed to examine the association of autoantibodies with the development and mortality of SRC. Kaplan-Meier survival analysis was performed comparing the groups classified by autoantibodies.ResultsAnti-centromere (n = 177/318, 56%), anti-topoisomerase I (n = 80/311, 26%), anti-RNA polymerase III (n = 27/204, 13%), and anti-U1-RNP (n = 24/305, 8%) were found in SSc patients (n = 330). SRC was observed in 24 out of 330 SSc patients, including anti-topoisomerase I (n = 12/24, 50%), anti-RNA polymerase III (n = 7/24, 29%), anti-U1-RNP (n = 5/24, 21%), and anti-centromere (n = 3/24, 13%). Anti-U1-RNP (odds ratio [95% confidence interval], 3.63 [1.11–10.2]), anti-RNA polymerase III (3.29 [1.16–8.70]), and anti-topoisomerase I (3.22 [1.37–7.57]) were associated with the development of SRC. All patients with SRC were treated with ACE inhibitors and the 1-year survival rate was 54%. Anti-topoisomerase I was associated with the 1-year mortality of SRC (6.00 [1.11–41.1]). When the survival rate was compared between the patients positive for anti-topoisomerase I (n=12) and negative for anti-topoisomerase I (n=12), the 1-year survival rate was 33% vs 75% (p=0.041), respectively (Figure 1A). Furthermore, the 1-year survival of anti-centromere (100%), anti-RNA polymerase III (83%), and others/not detected (50%) were shown in patients negative for anti-topoisomerase I (Figure 1B).Figure 1.Overall survival of patients with SRC according to the type of autoantibodies.(A) The survival rates in SRC patients who were positive for anti-topoisomerase I (solid line, n = 12) and those who were negative for anti-topoisomerase I (dotted line, n = 12).(B) SRC patients negative for anti-topoisomerase I were classified as patients with anti-RNA polymerase III (dotted line, n = 6), anti-centromere (broken line, n = 2), and others/not detected (chain line, n = 4).ConclusionSpecific SSc-related autoantibodies were associated with the morbidity and mortality in SRC.

Autoantibody profiles associated with morbidity and mortality in scleroderma renal crisis

The aim of this study was to investigate association of autoantibodies with scleroderma renal crisis (SRC) among Japanese patients. The clinical characteristics and mortality of 330 patients with sytemic screlosis (SSc) at Kyoto University Hospital were retrospectively analysed, focusing on possible association with anti-topoisomerase I (anti-topo I), anti-centromere (ACA), anti-RNA polymerase III (RNAPIII) and/or anti-U1-RNP. Logistic regression analyses were performed to reveal any association of these autoantibodies with the development and mortality of SRC. SRC was observed in 24 out of 330 SSc patients, including patients with anti-topo I (n = 12/24, 50%), anti-RNAPIII (n = 7/24, 29%), anti-U1-RNP (n = 5/24, 21%) and ACA (n = 3/24, 13%). Anti-U1-RNP [odds ratio (95% CI), 3.63 (1.11, 10.2)], anti-topo I [3.22 (1.37, 7.57)] and anti-RNAPIII (3.29 [1.16, 8.70]) were associated with the development of SRC. Furthermore, anti-topo I [6.00 (1.11, 41.1)] was associated with 1-year mortality of SRC. The 1-year survival rate after the onset of SRC among all patients and among those positive for anti-topo I was 54% and 33%, respectively. In contrast, the survival rate in patients negative for anti-topo I was 75%, of which the survival rate of patients positive for anti-RNAPIII and ACA was 83% and 100%, respectively. Specific SSc-related autoantibodies were associated with the morbidity and mortality of SRC.

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

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.

Successful treatment using rituximab in a patient with refractory polymyositis complicated by scleroderma renal crisis

Corticosteroids are the first-line treatment for patients with inflammatory myopathies. Myositis can be a clinical feature of scleroderma (polymyositis–scleroderma overlap syndrome), and treatment of this syndrome is a challenge for...

Clinical and immunologic predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies.

To identify predictive factors for scleroderma renal crisis (SRC) in patients with anti-RNA polymerase III (anti-RNAP III) antibodies. A total of 583 adult Japanese patients with systemic sclerosis (SSc) were screened for anti-RNAP III using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RNAP subsets were further identified by immunoprecipitation (IP) assays. The association of clinical and immunologic factors with SRC was examined by logistic analyses. In this cohort, 37 patients (6%) were positive for anti-RNAP III, as determined by anti-RNAP III-specific ELISA. Further IP assays revealed that 19 patients were positive for anti-RNAP I/III, 17 for anti-RNAP I/II/III, and 1 for anti-RNAP III. SRC occurred in a total of 17 (2.9%) of 583 patients, with a significantly higher frequency in anti-RNAP III-positive SSc patients (9 of 37 [24%]) than those without anti-RNAP III (8 of 546 [1%]) (odds ratio [OR] 21.6 [95% confidence interval (95% CI) 7.8-60.3], P < 0.00001). Our multivariate analyses using the Cox proportional hazards regression model revealed that anti-RNAP I/II/III positivity (OR 11.0 [95% CI 1.6-222.8], P = 0.0118) and an ELISA index for anti-RNAP III of ≥157 (OR 2.4 × 10(9) [95% CI 2.1-uncalculated], P = 0.0093) were independent factors associated with the development of SRC. Our findings indicate that anti-RNAP III is associated with SRC, as reported previously. In addition, the presence of anti-RNAP II in combination with anti-RNAP I/III (anti-RNAP I/II/III) and a higher ELISA index for anti-RNAP III may be associated with the development of SRC in SSc patients with anti-RNAP III.

Scleroderma Renal Crisis Following Widespread Application of Topical Triamcinolone

A 52-year-old patient with early diffuse scleroderma (Scl) developed scleroderma renal crisis (SRC) following exposure to topical steroid cream. She had applied a larger-than-prescribed quantity of triamcinolone acetonide 0.1% cream all over her body for 3 months, the absorption of the cream being the equivalent of 7.5 mg of oral prednisone per day. Her SRC was subsequently managed successfully with aggressive antihypertensive therapy and hemodialysis, and she was discharged home. High-dose corticosteroids (CS) have long been implicated in the development of SRC, but topical and low-dose CS until now have not. In our opinion, low-dose CS and a predisposing clinical setting appeared sufficient to provoke SRC and may broaden the proscription against CS in Scl.

Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis.

To determine whether the initiation of corticosteroids or other types of therapy affects the development of scleroderma renal crisis (SRC). Using a case-control study, 110 patients with systemic sclerosis who developed SRC between 1981 and 1993 were closely matched with controls on sex, race, age, disease duration, skin score, levels of creatine phosphokinase, and presence of tendon friction rubs. Corticosteroid use was determined prior to the onset of SRC in cases or prior to the first visit in controls. Cases were compared with matched controls using McNemar's matched-pair analysis and conditional logistic regression analysis. The effects of other drugs, including D-penicillamine, nonsteroidal antiinflammatory drugs (NSAIDs), calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors, were also evaluated. In the 6 months prior to SRC onset or to the first visit, high-dose corticosteroids (> or =15 mg/day prednisone or equivalent) were administered significantly more frequently in SRC patients (36%) than in the controls (12%) (McNemar's odds ratio 4.37, 95% confidence interval 2.03-9.43, P < 0.0001). New use of low-dose steroids, continuous use of any steroid dose, NSAIDs, calcium channel blockers, and ACE inhibitors were not associated with an increased risk of SRC. Antecedent D-penicillamine therapy may have been protective against the development of SRC in controls. This retrospective case-control study has shown a significant association between antecedent high-dose corticosteroid therapy and the development of SRC. These results should discourage the use of high-dose corticosteroids in patients with early diffuse scleroderma who are at increased risk of developing SRC.