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1.
Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.
Tsiogkas, SG, Grammatikopoulou, MG, Gkiouras, K, Zafiriou, E, Papadopoulos, I, Liaskos, C, Dardiotis, E, Sakkas, LI, Bogdanos, DP
Nutrients. 2021;(12)
Abstract
Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.
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2.
Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents.
Priora, M, Realmuto, C, Parisi, S, Ditto, MC, Borrelli, R, Peroni, CL, Laganà, A, Fusaro, E
Minerva gastroenterologica e dietologica. 2020;(3):280-289
Abstract
Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.
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3.
Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.
Zou, J, Thornton, C, Chambers, ES, Rosser, EC, Ciurtin, C
Frontiers in immunology. 2020;:616483
Abstract
Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
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4.
Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: A systematic review and meta-analysis.
Franco, AS, Freitas, TQ, Bernardo, WM, Pereira, RMR
Medicine. 2017;(23):e7024
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Abstract
BACKGROUND Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. METHODS MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. RESULTS Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). CONCLUSION Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.
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Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).
Cooper, C, Bardin, T, Brandi, ML, Cacoub, P, Caminis, J, Civitelli, R, Cutolo, M, Dere, W, Devogelaer, JP, Diez-Perez, A, et al
Aging clinical and experimental research. 2016;(1):1-16
Abstract
PURPOSE This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.
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[Periodontal disease in pediatric rheumatic diseases].
Fabri, GM, Savioli, C, Siqueira, JT, Campos, LM, Bonfá, E, Silva, CA
Revista brasileira de reumatologia. 2014;(4):311-7
Abstract
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity.
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Air pollution in autoimmune rheumatic diseases: a review.
Farhat, SC, Silva, CA, Orione, MA, Campos, LM, Sallum, AM, Braga, AL
Autoimmunity reviews. 2011;(1):14-21
Abstract
Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases.
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Clinical pharmacology of gold.
Kean, WF, Kean, IR
Inflammopharmacology. 2008;(3):112-25
Abstract
Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.
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Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects.
Setty, AR, Sigal, LH
Seminars in arthritis and rheumatism. 2005;(6):773-84
Abstract
OBJECTIVE To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications. METHODS Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed. RESULTS This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis. CONCLUSIONS Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities. RELEVANCE The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases.