Clinical manifestations and genetic susceptibility of extracranial giant cell arteritis

RESUMEN: La arteritis de células gigantes (ACG) es una vasculitis de grandes vasos que constituye la vasculitis más frecuente en pacientes mayores de 50 años en nuestro medio. Actualmente se describen dos patrones clínicos: el fenotipo craneal clásico y el más recientemente descrito fenotipo extracraneal. La ACG extracraneal, en comparación con la ACG craneal clásica, habitualmente debuta a edades más jóvenes y a menudo se manifiesta con un cuadro polimiálgico refractario que puede asociarse a síndrome general y síntomas atípicos, como predominio de clínica polimiálgica en cintura pelviana, dolor lumbar inflamatorio y claudicación en miembros. Estas diferencias plantean si la susceptibilidad genética en pacientes con ACG extracraneal es diferente a la de los pacientes con ACG craneal clásica. El estudio realizado revela que la ACG craneal y la ACG extracraneal comparten una misma asociación de susceptibilidad genética con genes HLA de clase II y de clase I; específicamente con HLA-DRB1*04:01 y HLA-B*15:01. Estos alelos tienen un efecto aditivo a la hora de aumentar el riesgo de ACG, independientemente del fenotipo clínico. Los haplotipos de VEGF (CGC y CGT) se asocian a mayor riesgo de manifestaciones isquémicas tanto en la ACG craneal como en la ACG extracraneal, pero no tienen influencia en el desarrollo de los dos diferentes fenotipos clínicos.ABSTRACT: Giant cell arteritis (GCA) is a large-vessel vasculitis that is the most common vasculitis among patients over 50 years of age in our setting. Two different clinical patterns of GCA have been described: the classic cranial phenotype and the more recently described extracranial phenotype. Compared with cranial GCA, patients with the extracranial GCA phenotype are often younger and more commonly present with refractory polymyalgia symptoms associated with constitutional syndrome and atypical manifestations such as predominant pelvic girdle involvement, inflammatory low back pain and limb claudication. These differences suggest that a different genetic susceptibility may exist in cranial and extracranial GCA. The study carried out reveals that cranial and extracranial GCA share the same association with HLA class II and class I genes; specifically with HLA-DRB1*04:01 and HLA-B*15:01. These alleles additively increase the risk of GCA, regardless of the clinical phenotype. VEGF haplotypes (CGC and CGT) are related to an increased risk of severe ischemic complications in both cranial and extracranial GCA but have no effect on the clinical phenotype expression of GCA

New amphiphilic amino acid derivatives for efficient DNA transfection in vitro

Nucleic acids-based therapies have recently developed as next-generationagents for treating and preventing viral infection, cancer, and genetic disorders,but their use is still limited due to its relatively poor delivery into targetedcells. We designed and synthesized new amphiphilic amino acid derivatives(cysteine-based) of low molecular weight, formed by the same pentapeptide(AG2: WWCOO) N-acylated, with different hydrophobic chains containingfrom 12 to 18 carbons, named AG2-Cn (N), which dimerize by oxidationin the presence of pLenti-CMV-GFP Puro plasmid (P) in the respectivegemini. We determined transfection efficiency, critical micelle concentration,particle size, ζ-potential and cytotoxicity for the derivatives obtained. Wefound that all the synthesized compounds were active for DNA delivery andhad greater ability to transfect CHO-K1 cells. In particular, AG2-C18 is apromising carrier for gene delivery because it showed no cytotoxicity and itsactivity was greater than or equal to the commercial actives currently used.Fil: Peña, Lucía Carolina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Argarañá, María Fernanda. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: de Zan, María Mercedes. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Giorello, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera". Universidad Nacional del Litoral. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera"; ArgentinaFil: Antuña, Sebastián. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Prieto, Claudio. Universidad Nacional del Litoral; ArgentinaFil: Veaute, Carolina Melania Isabel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Muller, Diana. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Caracterización de un instrumento con recomendaciones para la intervención de los factores psicosociales, en el componente extralaboral dirigido a los empleados de la empresa Teo – Farms SAS.

Caracterizar un instrumento que permita intervenir el componente extralaboral, de los factores psicosociales, de los trabajadores de la empresa Teo-Farms SAS.La responsabilidad en toda organización es velar por la salud integral de sus trabajadores a través de los diferentes planes de trabajo, esquemas de capacitaciones y la creación de sistemas de vigilancia epidemiológica entre otros, implementados desde el sistema de gestión de seguridad y salud en el trabajo. Dentro de este campo de la salud, cabe destacar la importancia y atención que merecen los Factores psicosociales debido a su gran incidencia en la población trabajadora, lo que deriva en el índice de ausentismo laboral y las incapacidades que se dan por las enfermedades de origen laboral que se puedan presentar, afectándose tanto el componente intralaboral como extralaboral. A través de esta investigación se buscó establecer los pilares de la problemática que desencadenan los factores de Riesgo Psicosocial en la empresa Teo – Farms SAS e inciden en el deterioro de la salud de los trabajadores por la aparición del estrés. Y una vez conocida la problemática, se generaron estrategias para evitar y/o minimizar la afectación en la salud por la exposición a factores de riesgo psicosocial.The responsibility in every organization is to ensure the integral health of its workers through the different work plans, training schemes and the creation of epidemiological surveillance systems among others, implemented from the health and safety management system at work . Within this field of health, it is important to highlight the importance and attention that psychosocial factors deserve due to their high incidence in the working population, which leads to the rate of absenteeism from work and the disabilities that are given by Occupational diseases that may occur, affecting both the intralaboral and extralabor component. Through this research we sought to establish the pillars of the problem that trigger Psychosocial Risk factors in the company Teo - Farms SAS and affect the deterioration of workers' health due to the appearance of stress. And once the problem was known, strategies were generated to avoid and / or minimize the impact on health due to exposure to psychosocial risk factors

Caracterización de un instrumento con recomendaciones para la intervención de los factores psicosociales, en el componente extralaboral dirigido a los empleados de la empresa Teo – Farms SAS.

Caracterizar un instrumento que permita intervenir el componente extralaboral, de los factores psicosociales, de los trabajadores de la empresa Teo-Farms SAS.La responsabilidad en toda organización es velar por la salud integral de sus trabajadores a través de los diferentes planes de trabajo, esquemas de capacitaciones y la creación de sistemas de vigilancia epidemiológica entre otros, implementados desde el sistema de gestión de seguridad y salud en el trabajo. Dentro de este campo de la salud, cabe destacar la importancia y atención que merecen los Factores psicosociales debido a su gran incidencia en la población trabajadora, lo que deriva en el índice de ausentismo laboral y las incapacidades que se dan por las enfermedades de origen laboral que se puedan presentar, afectándose tanto el componente intralaboral como extralaboral. A través de esta investigación se buscó establecer los pilares de la problemática que desencadenan los factores de Riesgo Psicosocial en la empresa Teo – Farms SAS e inciden en el deterioro de la salud de los trabajadores por la aparición del estrés. Y una vez conocida la problemática, se generaron estrategias para evitar y/o minimizar la afectación en la salud por la exposición a factores de riesgo psicosocial.The responsibility in every organization is to ensure the integral health of its workers through the different work plans, training schemes and the creation of epidemiological surveillance systems among others, implemented from the health and safety management system at work . Within this field of health, it is important to highlight the importance and attention that psychosocial factors deserve due to their high incidence in the working population, which leads to the rate of absenteeism from work and the disabilities that are given by Occupational diseases that may occur, affecting both the intralaboral and extralabor component. Through this research we sought to establish the pillars of the problem that trigger Psychosocial Risk factors in the company Teo - Farms SAS and affect the deterioration of workers' health due to the appearance of stress. And once the problem was known, strategies were generated to avoid and / or minimize the impact on health due to exposure to psychosocial risk factors

Treatment of giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in adults. Cranial manifestations are typical clinical features of this vasculitis. Sometimes the presenting symptoms are nonspecific and, in some cases, large-vessel involvement may prevail. Polymyalgia rheumatica is a frequent manifestation that in some cases may be the presenting symptom of GCA. Visual complications, in particular the risk of blindness, constitute the most feared manifestations of GCA. Prompt recognition of this vasculitis is required to avoid irreversible complications. Prednisone/prednisolone at a dose of 40-60?mg/day is the cornerstone therapy in GCA. Glucocorticoids lead to rapid improvement of symptoms and may reduce the risk of irreversible visual loss. However, relapses are common when the prednisone dose is tapered. Therefore, additional therapies are required in relapsing GCA or when a rapid reduction of glucocorticoids is needed. The most widely used conventional immunosuppressive drug is methotrexate Adjunctive treatment with methotrexate may decrease the risk of relapses and reduce glucocorticoid exposure. However, comprehensive reviews indicate that the efficacy of methotrexate in GCA is modest. The experience with other conventional immunosuppressive drugs in GCA patients is scarce. In some cases, the new biologic agents are required. Among them, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody tocilizumab. It improves clinical symptoms, reduce the cumulative prednisone dose and the frequency of relapses in GCA patients. However, anti-tumor necrosis factor-? therapy is not useful in GCA. Promising results on other biologic agents, such as abatacept, ustekinumab or anakinra, require further confirmatory studies

Tocilizumab in refractory Caucasian Takayasu’s arteritis: a multicenter study of 54 patients and literature review

Arteritis de Takayasu; Tocilizumab; Teràpia biològicaArteritis de Takayasu; Tocilizumab; Terapia biológicaTakayasu’s arteritis; Tocilizumab; Biological therapyObjective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu’s arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5–50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0–31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5–50.0) to 5.0 (0.0–5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0–14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0–46.0) versus 45.0 (38.0–57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0–38.0) versus 6.0 (1.0–23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7–5.6) versus 1.3 (0.3–3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors

Imaging Tests in the Early Diagnosis of Giant Cell Arteritis

Early recognition of giant cell arteritis (GCA) is crucial to avoid the development of ischemic vascular complications, such as blindness. The classic approach to making the diagnosis of GCA is based on a positive temporal artery biopsy, which is among the criteria proposed by the American College of Rheumatology (ACR) in 1990 to classify a patient as having GCA. However, imaging techniques, particularly ultrasound (US) of the temporal arteries, are increasingly being considered as an alternative for the diagnosis of GCA. Recent recommendations from the European League Against Rheumatism (EULAR) for the use of imaging techniques for large vessel vasculitis (LVV) included US as the first imaging option for the diagnosis of GCA. Furthermore, although the ACR classification criteria are useful in identifying patients with the classic cranial pattern of GCA, they are often inadequate in identifying GCA patients who have the extracranial phenotype of LVV. In this sense, the advent of other imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET)/CT, has made it possible to detect the presence of extracranial involvement of the LVV in patients with GCA presenting as refractory rheumatic polymyalgia without cranial ischemic manifestations. Imaging techniques have been the key elements in redefining the diagnostic work-up of GCA. US is currently considered the main imaging modality to improve the early diagnosis of GCA

Unmet needs in the management of cardiovascular risk in inflammatory joint diseases

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.MA González-Gay’s research has been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, PI12/00060, PI15/00525,PI18/00043, and RD12/0009/0013 and RD16/0012 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain), co-funded by FEDER funds

Moderate and High Disease Activity Predicts the Development of Carotid Plaque in Rheumatoid Arthritis Patients without Classic Cardiovascular Risk Factors: Six Years Follow-Up Study

Patients with rheumatoid arthritis (RA) have a higher incidence of subclinical atherosclerosis and cardiovascular (CV) disease. It is postulated that the appearance of accelerated atherosclerosis in these patients is a consequence of the inflammation present in the disease. In this study, we aim to determine if baseline disease activity in patients with RA predicts the future development of carotid plaque. A set of consecutive RA patients without a history of CV events, cancer or chronic kidney disease, who did not show carotid plaque in a carotid ultrasound assessment, were prospectively followed up for at least 5 years. At the time of recruitment, CV risk factors and disease-related data, including disease activity scores, were assessed. At the end of the follow-up, a carotid ultrasound was repeated and patients were divided into two groups; those who developed carotid plaque, and those who did not. A multivariable regression analysis was performed to define the predictors for the development of carotid plaque. One hundred and sixty patients with RA were followed up for an average of 6 ± 1 years. After this time, 66 (41%) of the patients had developed carotid plaque, and 94 (59%) did not. Patients with carotid plaque were significantly older (47 ± 13 vs. 55 ± 9 years, p < 0.001) at baseline, were more frequently diabetic (0% vs. 6%, p = 0.028), and had higher total cholesterol (197 ± 36 vs. 214 ± 40 mg/dL, p = 0.004) and LDL cholesterol (114 ± 35 vs. 126 ± 35 mg/dL, p = 0.037) at the beginning of the study. After multivariable adjustment, patients who were in the moderate and high disease activity (DAS28-CRP) categories displayed a higher odds ratio for the appearance of carotid plaque (OR 2.26 [95% CI 1.02?5.00], p = 0.044) compared to those in the DAS-28-CRP remission category. Remarkably, when patients were divided in patients within the low-risk SCORE category, and patients included in the remaining SCORE categories (moderate, high and very high), the relation between DAS28-CRP and the development of carotid plaque was only significant in the low-risk SCORE category. In conclusion, disease activity predicts the future development of subclinical atherosclerosis in patients with RA

Coexisting sarcoidosis and systemic lupus erythematosus: a case report and literature review

The coexistence of sarcoidosis and SLE in the same patient has uncommonly been reported. Information on the epidemiology, clinical presentation, and management of this rare association is scarce. We report a 46-year-old Hispanic man who was recently diagnosed with concomitant SLE and sarcoidosis at our institution. A diagnosis of sarcoidosis was established due to the presence of dyspnea, fever, and malaise along with bilateral hilar lymphadenopathy and histological evidence of non-caseating granuloma. In addition, he fulfilled the American Rheumatism Association (ACR) criteria for SLE due to a history of photosensitivity, polyarthritis, lymphocytopenia, and positivity of ANA and anti-dsDNA antibodies. He was successfully treated with a combination of oral glucocorticoids, hydroxychloroquine, and methotrexate. In a further step, we conducted an extensive literature review to further investigate into the association of sarcoidosis and SLE. We identified 25 additional published cases. The concurrence of these two conditions may be more common than previously reported, mainly affecting young female adults in the fourth decade of life. The most common manifestation of sarcoidosis was mild pulmonary symptoms whereas SLE presentation was highly variable. Most patients were positive for anti-dsDNA antibodies. Different therapeutic strategies included oral glucocorticoids, hydroxychloroquine, conventional immunosuppressive drugs and, cyclophosphamide in severe cases. Our study reinforces the need of considering the potential concurrence of sarcoidosis and SLE. Clinicians should be aware of the potential presence of SLE in patients with a diagnosis of sarcoidosis presenting with cutaneous manifestations, cytopenia, renal involvement, and/or positivity for ANA and anti-dsDNA antibodies