Correlation between endothelial function and carotid atherosclerosis in rheumatoid arthritis patients with long-standing disease

Introduction In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease. Methods One hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of CV disease and had at least one year of follow-up after disease diagnosis were randomly selected. Brachial and carotid ultrasonography were performed to determine FMD and carotid IMT, respectively. Results Carotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis. Patients with a disease duration ≤ 7 years had significantly lower carotid IMT (mean ± SD) 0.69 ± 0.17 mm than those with long disease duration (0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up). Also, patients with a long disease duration had severe endothelial dysfunction (FMD 4.0 ± 4.0% in patients with disease duration from 14.5 to 19.7 years) compared with those with shorter disease duration (FMD 7.4 ± 3.8% in patients with disease duration ≤ 7 years). Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients. However, carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years (P = 0.02). Conclusions In patients with RA without CV disease, endothelial dysfunction and carotid IMT increased with the duration of RA. The association between FMD and carotid IMT values was observed only in patients with long disease duration

Giant cell arteritis: is the clinical spectrum of the disease changing?

Background: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects patients aged over 50 years. It can show a typical clinical picture consisting of cranial manifestations but sometimes nonspecific symptoms and large-vessel involvement prevail. Prompt diagnosis and treatment is essential to avoid irreversible damage. Discussion: There has been an increasing knowledge on the occurrence of the disease without the typical cranial symptoms and its close relationship and overlap with polymyalgia rheumatica, and this may contribute to reduce the number of underdiagnosed patients. Although temporal artery biopsy is still the gold-standard and temporal artery ultrasonography is being widely used, newer imaging techniques (FDG-PET/TAC, MRI, CT) can be of valuable help to identify giant cell arteritis, in particular in those cases with a predominance of extracranial large-vessel manifestations. Conclusions: Giant cell arteritis is a more heterogeneous condition than previously thought. Awareness of all the potential clinical manifestations and judicious use of diagnostic tests may be an aid to avoid delayed detection and consequently ominous complications.This review was funded by Roche Farma S.A. Spain

Autoimmune rheumatic diseases

"The term autoimmune rheumatic diseases (ARDs) encompasses a heterogeneous group of conditions characterized by joint involvement along with a wide spectrum of systemic manifestations. The most common ARDs are rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Nevertheless, all these conditions share similar pathophysiological mechanisms [1, 2] and a common risk of developing a process of accelerated atherosclerosis [3]. In this regard, in this special issue J. Amaya-Amaya and colleagues discussed the mechanisms associated with the increased risk of cardiovascular disease (CVD) in patients with autoimmune diseases. These authors emphasize the relevance of the CVD in rheumatic conditions and its connection with inflammation and autoimmunity. They also highlight the need of a more aggressive management of these conditions, both of disease activity and classic cardiovascular risk factors. A good example of accelerated atherosclerosis in the setting of an ARD is SLE, in which endothelial dysfunction, an early step in the atherogenesis process, is observed before cardiovascular events can occur. With respect to this, A. Mak and N. Y. Kow performed a comprehensive review of the mechanisms that are involved in endothelial damage.These authors focused on the factors involved in endothelial damage and repair and, therefore, in the development of CVD in patients with SLE. They discussed the relevant role of factors such as type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia that along with the aberrant function of the endothelial progenitor cells lead to endothelial dysfunction and increased susceptibility to develop CVD in patients with SLE. Based on these lines of evidence, the authors’ claim is in favor of early intervention at the preclinical stage of atherogenesis in these patients

SCORE2 versus SCORE in patients with systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) has been associated with an increased risk of cardiovascular (CV) disease. Recently, the Systematic Coronary Risk Assessment (SCORE), a well-known CV risk algorithm, has been updated to a new predictive model (SCORE2). This new algorithm improves the identification of individuals at high risk of developing CV disease across Europe. Since carotid atherosclerosis is a predictor of future CV events and CV death, our objective was to compare the predictive capacity of SCORE2 versus SCORE for the presence of subclinical carotid atherosclerosis in patients with SLE. Methods: Two hundred and thirty-five individuals over 40 years of age diagnosed with SLE were consecutively recruited in this cross-sectional study. SCORE and SCORE2 were calculated. The relationship of SCORE and SCORE2 with each other, and with the presence of subclinical carotid atherosclerosis (both carotid plaque and carotid intima media thickness -cIMT-), was studied. Results: SCORE2 and SCORE did not correlate with each other (Spearman's Rho = 0.125, p = 0.065). Although SCORE did not correlate with cIMT (Spearman?s Rho = -0.022, p = 0.75), the correlation of SCORE2 with cIMT was statistically significant (Spearman?s Rho = 0.367, p < 0.001). Similarly, SCORE did not show significant discrimination for the presence of carotid plaque [AUC = 0.521 (95% CI = 0.443?0.600)], while SCORE2 did [AUC = 0.720 (95% CI = 0.656-0.785)]. The difference between AUCs was found to be statistically significant (p < 0.001), thus showing that the prediction capacity of SCORE2 was significantly higher than that of SCORE. Conclusion: In SLE patients, the ability of SCORE2 to predict the presence of subclinical atherosclerosis is higher than that of SCORE. According to our results, SCORE2, rather than SCORE, should be used in the CV risk stratification of patients with SLE. Prospective studies are needed to confirm these findings.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant to I.F.-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 and by Fondo Europeo de Desarrollo Regional-FEDER-(Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083, PI20/00084). Prof. González-Gay's research is supported by the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012)

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)

COVID-19 patients with psoriasis and psoriatic arthritis on biologic immunosuppressant therapy versus apremilast in North Spain

Immunosuppressive and immunomodulatory treatments are critical for the management of inflammatory and autoimmune conditions such as psoriasis or psoriatic arthritis. Similar to those illnesses, the lung injury and acute respiratory distress shown in coronavirus disease 2019 (COVID‐19) patients are the result of a disruption in the balance of pro‐ and anti‐inflammatory cytokines. This hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), associated with the severity of the coronavirus disease, is called the cytokine storm. There is a growing concern regarding how patients on immunosuppressant biologic therapies might be at higher risk of being infected and whether they need to discontinue their treatment preemptively. Clinical data on COVID‐19‐infected patients with psoriasis or psoriatic arthritis are still scarce. Here, we presented seven cases of these type of patients. The patient infected with COVID‐19 on apremilast and the one on apremilast with infected spouse showed the best safety profile and mildest symptoms. One of the secukinumab patients also presented a relatively good outcome. Infliximab patients and the one with serious comorbidities showed the worst outcome. Even though more clinical data are yet needed to draw strong conclusions, apremilast could be a safer alternative for dermatology and rheumatology patients in case of clinically important active infection

Lack of association between carotid intima-media wall thickness and carotid plaques and markers of endothelial cell activation in rheumatoid arthritis patients undergoing anti-TNF therapy

Introduction: To determine the relationship between biomarkers of endothelial cell activation, and carotid artery intima-media wall thickness (IMT) and plaques, two surrogate markers of atherosclerosis, in a series of rheumatoid arthritis (RA) patients undergoing anti-TNF therapy. Methods: 29 consecutive Spanish patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of cardiovascular (CV) disease, and had at least one year of follow-up after disease diagnosis were selected. All patients were undergoing anti-TNF-infliximab therapy because of severe disease refractory to conventional disease modifying antirheumatic drugs. Carotid ultrasonography was performed to determine IMT and carotid plaques. Levels of sICAM-3, sICAM-1, sVCAM-1, sPselectin and sE-selectin were assessed by ELISA immediately before an infusion of infliximab. Results: The median disease duration was 14 years. Despite infliximab, no patient experienced a disease remission (DAS28: median 4.17). Only a marginally significant correlation between sVCAM-1 and carotid IMT was observed when both total correlation using Spearman correlation coefficient (p= 0.08) or partial correlation adjusting for sex, age at the time of study, disease duration, rheumatoid factor, and classic CV risk factors was performed (p= 0.09). Also, no association between presence of carotid plaques and levels of biomarkers of endothelial cell activation was observed. Conclusion: In long-standing RA patients without CV disease undergoing anti-TNF therapy no association between levels of soluble markers of endothelial cell activation and carotid ultrasonography abnormalities was observed. Further studies are needed to establish the best tools to be used in the assessment of CV risk of RA.Acknowledgements. This study was supported by two grants from "Fondo de Investigaciones Sanitarias" PI06-0024 and PS09/00748 and by RETICS Program, RD08/0075 (RIER) from "Instituto de Salud Carlos III" (ISCIII