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

A Review of the Dermatological Complications of Giant Cell Arteritis

Giant cell arteritis (GCA) is characterized by granulomatous inflammation of large and medium-sized vessels. It is the most common vasculitis among elderly people in Europe and North America. GCA usually presents with ischemic cranial manifestations such as headache, scalp tenderness, visual manifestations, and claudication of the tongue and jaw. Thickness and tenderness of temporal arteries are the most recognizable signs of GCA on physical examination. Laboratory tests usually show raised acute phase reactants. Skin manifestations are uncommon in GCA and are rarely found as a presenting symptom of GCA. Necrosis of the scalp and tongue is the most common ischemic cutaneous manifestation of GCA. Although infrequent, when present it reflects severe affection and poor prognosis of GCA. Panniculitis-like lesions have been reported in the setting of GCA, with nodules being the most common finding. Other entities, such as generalized granuloma annulare or basal cell carcinoma have been occasionally described in GCA patients. Prompt recognition and initiation of therapy are crucial to prevent serious complications of GCA. When high suspicion of GCA exists, immediate administration of glucocorticoids is recommended. It is advisable to refer the patient to a specialist GCA team for further multidisciplinary assessment.Funding: This line of research on vasculitis was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/ 0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

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

The role of biologics in the treatment of giant cell arteritis

ABSTRACT: Introduction: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects individuals older than 50 years. Although glucocorticoids remain the mainstay in the treatment of this vasculitis, other drugs are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main biologic therapies used for the managements of GCA. Expert commentary: Although several biologic agents have been used in patients with GCA, the only biologic agent currently approved for this purpose is the recombinant humanized anti-IL-6 receptor antibody: tocilizumab. It has demonstrated efficacy to improve clinical symptoms, decrease the cumulative prednisone dose and reduce the frequency of relapses in clinical trials and real-life studies on patients with GCA. A trial showed that abatacept may be useful to maintain remission in GCA patients. An openlabel study suggested that ustekinumab could be useful for the treatment of patients with refractory GCA. However, further studies are required to confirm if both abatacept and ustekinumab are useful as an adjunctive therapy to reduce relapses or as a glucocorticoid sparing agent in GCA. Anakinra has been successfully used in a few patients with refractory GCA. In contrast, anti-tumor necrosis factor- α therapy yielded disappointing results in GCA

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