Abnormalities In Scleroderma Research Articles

Investigating Novel Electrocardiographic Ventricular Repolarization Markers in Scleroderma Patients

Aim: Ventricular repolarization involves the J-wave, ST-segment, T-wave, and U-wave on the surface electrocardiography (ECG). QT dispersion, Tp-e interval, Tp-e/QT, Tp-e/QTc, Tp-e/JT, and Tp-e/JTc ratios are some indices that predict ventricular tachyarrythmias. Although studies, evaluating repolarization abnormalities in scleroderma have frequently focused on Tp-e interval, QT, and Tp-e/QT, in our study, we aimed to investigate the risk of ventricular arrhythmia by using Tp-e/JT and Tp-e/JTc ratios, which are relatively new parameters.Methods: The study comprised 42 patients with scleroderma (mean age: 50.8 ± 7.3 years; 38 women and 4 men) and 40 healthy controls (mean age: 47.9 ± 5.5 years; 37 women and 3 men). We leveraged a standard 12-lead ECG recording to measure Tp-e interval, Tp-e/JT, Tp-e/JTc, Tpe/QTc, and Tp-e/QT parameters for each patient.Results: Compared to the scleroderma patients electrocardiographic repolarization parameters including Tp-e (90.8 ± 10.9 vs 77.0 ± 10.2, p

PULMONARY FUNCTION TEST PARAMETERS IN DIFFUSE AND LIMITED SCLERODERMA

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Scleroderma is characterized by varying degrees of organ fibrosis and obliterative vasculopathy. Lung involvement is the leading cause of morbidity in Scleroderma. The spectrum of Pulmonary Function Test (PFT) abnormalities in Scleroderma has been reported to be variable, with a recent study revealing that PFTs have a low sensitivity in detecting Scleroderma-related interstitial lung disease, with false negative cases more common in diffuse Scleroderma. The objectives of this study are to determine the spectrum of PFT abnormalities in Scleroderma and to compare PFTs in limited and diffuse Scleroderma. METHODS: We reviewed the records of 174 Scleroderma patients followed at the rheumatology clinic in our institution. Patient demographics and PFT parameters [FEV1, FVC, FEV1/FVC, TLC and DLCO percent predicted (%)] were noted in patients with limited (Scl-Ltd) and diffuse (Scl-Diffuse) disease. Obstruction was defined as FEV1/FVC < 70%; restriction as TLC < 80% and impaired diffusion as DLCO < 80%. Severity of restriction was defined per ATS criteria. PFT parameters in the two groups were compared by Student’s t-test. p < 0.05 was deemed statistically significant. RESULTS: Mean age: 65 +/- 12.2 years; 91% were females; 76.4% had Scl-Ltd. Mean FEV1 was: 92 +/- 22%; mean FVC: 88.5 +/- 21.3%; mean TLC: 91.5 +/- 18%; mean DLCO:70.5 +/- 23%. Twenty-eight % patients had normal PFTs; 12 % had obstruction, 32% had restriction and 28% patients had isolated reduction in DLCO. Thirty-five % patients with Scl-Ltd and 24.4% patients with Scl-Diffuse had a normal DLCO. In patients with restriction, 40% had mild, 51% moderate and 9% had severe restriction. PFT abnormalities were seen in 37.6% Scl-Ltd, and 56% Scl-Diffuse. PFT parameters in the 2 groups are shown below. PFT parameters in 2 groups (Table) CONCLUSIONS: Majority of Scleroderma-patients have abnormal PFTs. Restriction and impairment in diffusion were the most common abnormalities. Over 1/3rd patients with limited disease had PFT abnormalities. CLINICAL IMPLICATIONS: Whether restriction defined by TLC corelates with fibrosis on imaging need to be studied. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Carol Halasan, source=Web Response No relevant relationships by Sophie Korzan, source=Web Response

Primary Cardiac Involvement in Scleroderma and Role of Cardiac MRI

Systemic sclerosis (scleroderma) is a connective tissue disease characterized by vascular dysfunction and fibrosis that can affect multiple organ systems. We present case of primary cardiac involvement and the diagnostic role of cardiac MRI. Cardiovascular magnetic resonance imaging (MRI) is an accurate, quantitative method for the non-invasive assessment of myocardial perfusion. The presence of clinically apparent myocardial involvement in scleroderma portends a very poor prognosis. One study of US veterans found that clinical cardiac disease in scleroderma was associated with a 70% mortality rate at five years. Management of heart failure and conduction system abnormalities in scleroderma is similar to other cardiac disease. It includes afterload reduction, beta-blockade, defibrillator placement, etc. Patients with reduced cardiac function and normal coronary arteries may benefit from increased immune suppresion.

The heart and pulmonary vasculature in scleroderma: clinical features and pathobiology.

For nearly 50 years there have been concerns that scleroderma affects the heart. The two main mechanisms that are thought to be involved are; a fibrotic process secondary to myocardial Raynaud phenomenon (RP) or an immune-mediated myocarditis. In the past year several studies have been published that confirm the frequent occurrence of subclinical cardiac abnormalities in scleroderma. These studies do not tend to support the myocardial RP theory and raise doubts about the prognostic significance of these minor abnormalities. Involvement of the lungs in the form of pulmonary hypertension affects between 7-50% of patients with scleroderma. Until the past year this has been regarded by most as an untreatable condition associated with an inexorable decline. Epoprostenol therapy has now been proven beneficial in a randomized clinical trial, and several other agents show promise in the treatment of this condition. Furthermore, it is becoming apparent that lung transplantation is as successful in patients with scleroderma, as it is in primary pulmonary hypertension.

Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma.

Vascular abnormalities in scleroderma are fundamental to the pathogenesis of this disease. The objective of this study was to characterize dermal microvascular endothelial cells (DMEC) isolated from scleroderma patients with respect to growth and expression of the constitutive form of endothelial nitric oxide synthase (eNOS). DMEC from patients with both systemic sclerosis (SSc) and localized scleroderma (Loc Scl) contained small intact microvascular structures in contrast to single cell isolations obtained from control skin. Immunoaffinity selection on anti-PECAM-1 beads yielded pure populations of DMEC expressing normal markers. While the morphology and initial growth of SSc DMEC closely paralleled control cells, the growth of SSc DMEC decreased with time in culture (doubling time of 3 days vs. 5 days). Expression of ecNOS mRNA was reduced in both Loc Scl and SSc as shown by semi-quantitative RT-PCR (p < 0.001). Western blots showed variable but generally lower ecNOS protein levels and decreased levels of nitrogen oxides in media were found from both SSc and Loc Scl relative to control cells. The results indicate an intrinsic defect in the mechanism of nitric oxide production in DMEC isolated from scleroderma patients and suggest its possible involvement in the pathophysiology of scleroderma.

Immunologic abnormalities in scleroderma.

The immune system abnormalities of scleroderma are diverse and in association with vascular and mesenchymal cell abnormalities, contribute to the organ system dysfunction and clinical expression of the disease. Recent insights into novel immune regulatory pathways, immune reactivity to self-antigens, and the potential association of persistent fetal cells and disease expression may serve to increase our understanding of this enigmatic disease.

Vascular abnormalities in scleroderma.

Vascular abnormalities represent a fundamental event in the pathogenesis of systemic sclerosis. This review focuses on key observations that support this view and builds a framework with which to clarify our understanding of how endothelial cell damage may trigger a self-fueling process ending in pathological tissue fibrosis in those susceptible to scleroderma. The studies reviewed in this article pertain to systemic sclerosis patients.

Hematological abnormalities in scleroderma. A study of 180 cases.

Hematological abnormalities in scleroderma indicate a specific complication of the disease itself, or an associated illness. Among 180 patients with scleroderma, anemia was detected in 25% and was attributed to chronic inflammatory disease (usually an overlap syndrome), bleeding mucosal telangiectases as part of the CREST syndrome, intestinal malabsorption, and microangiopathic hemolysis. Leukocytosis, present in 14%, was correlated with active myopathy and/or advanced visceral involvement while leukopenia was suggestive of a crossover with systemic lupus erythematosus. Thrombocytopenia was often a manifestation of microangiopathy, and thrombocytosis was associated with an arteritis or a tumor syndrome.

Letter: "Acute abdomen" with meningococcal meningitis.

Letter: "Acute abdomen" with meningococcal meningitis.

Esophageal motor abnormalities in scleroderma and related diseases.

Esophageal motor activity was measured by intra-esophageal pressure recordings in 53 patients with scleroderma and 29 patients with other collagen diseases. The purpose of the study was to determine the relationship of motor abnormalities to esophageal symptoms, to compare the abnormalities in scleroderma with those in other collagen diseases, and to try to increase understanding of the responsible mechanism. Methacholine was given to 36 of the 53 patients with scleroderma to confirm that the Mecholyl test is negative in scleroderma and to see whether intraluminal pressure changes accompany the resulting improvement in esophageal emptying. Abnormalities in the intraluminal pressure response of the esophagus to deglutition were seen in 79% of the patients with scleroderma. Of those with an abnormal swallowing pattern, 62% showed diminution or absence of the lower esophageal sphincter pressure zone. Although changes in swallowing pattern did not correlate with esophageal symptoms, absence of lower esophageal sphincter pressure did. The 29 patients with other collagen diseases had similar but less severe abnormalities in the motor response to deglutition. Usually there was better preservation of the lower esophageal sphincter. Neither abnormality correlated with esophageal symptoms in this group. The Mecholyl test was negative in patients with scleroderma. No significant change was found in the pressure studies after methacholine. Of the 66 patients who had both X-ray and manometric studies of the esophagus, intraluminal pressure studies showed aperistalsis in all patients without peristalsis on X-ray studies as well as in 18 patients who appeared to show normal esophageal peristalsis on X-ray studies.