Eleni Pagkopoulou

Bio: Eleni Pagkopoulou is an academic researcher from Aristotle University of Thessaloniki. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 5, co-authored 15 publications receiving 51 citations.

Comorbidity burden in systemic sclerosis: beyond disease-specific complications

Abstract: Systemic sclerosis (SSc) is a chronic, systemic disease characterized by fibrosis of the skin and internal organs, vasculopathy, and auto-immune activation. On the top of severe organ involvement such as interstitial lung and myocardial fibrosis, pulmonary hypertension, and renal crisis, individuals diagnosed with SSc may suffer from a number of comorbidities. This is a narrative review according to published recommendations and we searched the online databases MEDLINE and EMBASE using as key words the following terms: systemic sclerosis, scleroderma, myocardial fibrosis in combination with micro- and macro-vascular disease, cardiac involvement, atherosclerosis, cardiovascular disease and coronary arteries, infections, cancer, depression, osteoporosis, and dyslipidemia. Although data are usually inconclusive it appears that comorbidities with significant impact on life expectancy, namely cardiovascular disease, infections, and cancer as well as phycological disorders affecting emotional and mental health are highly prevalent in SSc population. Thereafter, the aim of this review is to summarize the occurrence and the clinical significance of such comorbidities in SSc population and to discuss how rheumatologists can incorporate the management of these conditions in daily clinical practice.

Arterial stiffness correlates with progressive nailfold capillary microscopic changes in systemic sclerosis: results from a cross-sectional study.

Abstract: While microangiopathy is well-documented in systemic sclerosis (SSc), a potential link between SSc and macrovascular disease is highly debated and remains to be established. The aim of the present study is to investigate the association between micro- and macrovascular involvement in the setting of SSc. Consecutive, consenting SSc patients were assessed by nailfold video-capillaroscopy (NVC) to evaluate the microcirculation. The number of capillaries per mm2 and the capillaroscopic skin ulcer risk index (CSURI) were measured, and findings were also classified into three scleroderma patterns (i.e., early, active, and late). Carotid intima-media thickness (IMT), aortic augmentation index corrected for a heart rate of 75 beats per minute (AIx-75), carotid-femoral pulse wave velocity (PWV), and central systolic and diastolic blood pressure were also determined to assess macrovascular function. A total of 37 patients were studied. A significant correlation was observed between AIx and the average number of capillaries per mm2 (r = − 0.34, p = 0.047) and between AIx and CSURI (r = 0.35, p = 0.044). Patients with the “early” scleroderma pattern had lower AIx values compared with “active” (20.5 ± 11.4 vs 34.1 ± 11.5%, p = 0.02) and “late” (20.5 ± 11.4 vs 33.4 ± 8.8%, p = 0.05) patterns. No other significant correlations were found between macrovascular biomarkers (PWV, carotid IMT, systolic and diastolic central blood pressure) and the capillaroscopic measurements. These data suggest that arterial stiffness (as assessed by AIx-75) correlates with microvascular damage in patients with SSc.

Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis.

Abstract: Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD). Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video capillaroscopy provides a thorough assessment of capillary density and functional reserve. This study aimed to examine possible differences in structural and functional capillary density in CKD stages 2–4 with nailfold video capillaroscopy. Ninety-six CKD patients, divided into four equally sized groups according to CKD stage (2, 3a, 3b, 4), underwent nailfold video capillaroscopy, during which capillary density was measured at baseline, after 4-min arterial occlusion and after 2-min venous occlusion. Arterial stiffness and wave parameters were measured with applanation tonometry and common carotid intima-media thickness (ccIMT) with ultrasound. Baseline capillary density showed a progressive reduction with advancing CKD stages (stage 2: 32.6 ± 2.8, stage 3a: 31.2 ± 3.8, stage 3b: 32.5 ± 3.3, stage 4: 28.5 ± 3.1, p = 0.011). Similar reductions were observed during postocclusive hyperemia (39.4 ± 3.0, 37.6 ± 4.2, 38.4 ± 3.8, and 33.8 ± 3.3, respectively; p = 0.021) and after venous congestion (41.1 ± 3.1, 39.0 ± 4.4, 39.9 ± 3.5, and 35.2 ± 3.4; p = 0.032). Office PWV and ccIMT showed nonsignificant increasing trends with advancing CKD. In multivariate analysis, eGFR showed a positive association (per ml/min increase; β: 0.053, 95% CI: 0.004–0.101), whereas diabetes (β: −1.706, 95% CI: −3.176 to −0.236) and parathyroid hormone (PTH) (per pg/ml increase; β: −0.022, 95% CI: −0.036 to −0.008) had negative associations with postocclusive capillary density. Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may largely contribute to the increased cardiovascular risk of CKD patients.

Pyoderma gangrenosum and pyogenic arthritis presenting as severe sepsis in a rheumatoid arthritis patient treated with golimumab

Abstract: Rheumatoid arthritis is a systemic autoimmune disease resulting in joint destruction and deformities, but also associated with extraarticular and systemic manifestations. The later devastating conditions, such as the development of rheumatoid vasculitis, are more frequently encountered in seropositive patients and their incidence has been attenuated after the introduction of biologic disease modifying drugs, such as anti-tumor necrosis factor alpha (TNFa) agents, which generally have considerably contributed to the better control and long-term outcomes of the disease. Interestingly, autoimmune syndromes may, rarely, present in patients without a positive history after the initiation of treatment. We present a rare case of a woman with seronegative rheumatoid arthritis who developed pyoderma gangrenosum whistle on treatment with golimumab, a fully humanized anti TNFa antibody. The recording of this as well as analogous paradoxical autoimmune syndromes in association with the individual patient characteristics will render treating physicians aware of potential adverse reactions and assist in the understanding of the cytokine driven pathophysiological mechanisms underlying these disorders.

Weak within-individual association of blood pressure and pulse wave velocity in hemodialysis is related to adverse outcomes.

Abstract: Objectives Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies in such patients showed that when BP decrease is accompanied by PWV decrease the survival is improved. This study examines the prognostic role of the mean BP (MBP)-PWV association for cardiovascular outcomes and all-cause mortality in hemodialysis. Methods A total of 242 hemodialysis patients underwent 48-h ambulatory BP monitoring with Mobil-O-Graph-NG and were followed for 33.17 ± 19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the β-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, nonfatal myocardial infarction or nonfatal stroke. Secondary end-points were all-cause mortality, cardiovascular mortality and a combination of cardiovascular events. Results Higher quartiles of β-coefficients (indicating strong within-individual association of MBP with PWV) were related to greater cumulative freedom from the primary end-point (50.8, 60.0, 70.0 and 80.3% for quartiles 1-4, respectively; log-rank P = 0.001), better overall survival (60.7, 61.7, 73.3, 86.9%; log-rank P = 0.002) and better cardiovascular survival (78.7, 75.0, 81.7, 91.8% for quartiles 1-4; log-rank P = 0.044). The future risks of the primary end-point, all-cause and cardiovascular mortality and the combined outcome were progressively increasing with lower quartiles of β-coefficients, indicating patients with weak MBP-PWV association (hazard ratios for all-cause mortality 3.395; 95% confidence interval: 1.524-7.563, P = 0.003 for quartile 1 vs. quartile 4). Conclusion Weaker within-individual MBP-PWV association, based on ABPM recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that arterial stiffness insensitive to BP changes is the underlying factor for adverse outcomes in these individuals.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

Abstract: Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Paradoxical skin reactions to biologics in patients with rheumatologic disorders

Abstract: Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

Abstract: Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

Biologic and small-molecule medications in the management of pyoderma gangrenosum.

Abstract: Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder characterized by neutrophil dysfunction. There are currently no FDA-approved drugs for the treatment of this disease, and treatment has typically relied on traditional immunosuppressive medications such as prednisone or cyclosporine. The efficacy of biologics in the treatment of other pro-inflammatory conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease is well-documented in the literature. Therefore, the use of biologic medications for the treatment of rarer inflammatory skin conditions, such as PG, is a compelling topic for investigation. Biologic and small-molecule therapies allow physicians to target specific pro-inflammatory mediators that underlie PG pathogenesis. This review provides an update on the use of biologic and small-molecule medications for the treatment of PG and summarizes the latest data on the clinical efficacy and pharmacology of these treatments.

Diagnosis and novel clinical treatment strategies for pyoderma gangrenosum

Abstract: Introduction: Pyoderma gangrenosum (PG) is a noninfectious, reactive inflammatory neutrophilic dermatosis that is commonly associated with autoimmune and neoplastic disorders. There are emerging diagnostic tools and treatment options for PG.Area covered: The diagnosis of PG should be seriously considered when managing ulcers to avoid unnecessary medical and surgical complications with prompt and suitable treatment. There are no standardized treatment guidelines for PG, and current therapy largely depends on the severity and progression of the disease. Systemic corticosteroids, immunosuppressant therapy, and biologic agents remain mainstay therapies. In this article, we present a literature review of recent diagnostic and novel treatment options for the management of PG. The literature research considered clinical studies or scientific reviews. Studies were identified by searching electronic databases and reference lists of respective articles till August 2019.Expert opinion: The true diagnosis of PG is challenging, as there is no diagnostic gold standard. PARACELSUS is a novel diagnostic tool. Biologics and small molecules are emerging systemic therapy options that are relatively new in treatment of PG.